CA2074527A1 - Dietary supplements comprising vitamins and minerals - Google Patents
Dietary supplements comprising vitamins and mineralsInfo
- Publication number
- CA2074527A1 CA2074527A1 CA002074527A CA2074527A CA2074527A1 CA 2074527 A1 CA2074527 A1 CA 2074527A1 CA 002074527 A CA002074527 A CA 002074527A CA 2074527 A CA2074527 A CA 2074527A CA 2074527 A1 CA2074527 A1 CA 2074527A1
- Authority
- CA
- Canada
- Prior art keywords
- vitamin
- supplement
- dietary
- daily
- supply
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 229910052500 inorganic mineral Inorganic materials 0.000 title claims abstract description 65
- 239000011707 mineral Substances 0.000 title claims abstract description 65
- 235000015872 dietary supplement Nutrition 0.000 title claims abstract description 24
- 229940088594 vitamin Drugs 0.000 title abstract description 128
- 239000011782 vitamin Substances 0.000 title abstract description 128
- 229930003231 vitamin Natural products 0.000 title abstract description 101
- 235000013343 vitamin Nutrition 0.000 title abstract description 101
- 239000013589 supplement Substances 0.000 claims abstract description 60
- 238000000034 method Methods 0.000 claims abstract description 55
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 53
- 239000003963 antioxidant agent Substances 0.000 claims abstract description 51
- 150000001413 amino acids Chemical class 0.000 claims abstract description 23
- ZTHYODDOHIVTJV-UHFFFAOYSA-N Propyl gallate Chemical compound CCCOC(=O)C1=CC(O)=C(O)C(O)=C1 ZTHYODDOHIVTJV-UHFFFAOYSA-N 0.000 claims description 62
- 235000010755 mineral Nutrition 0.000 claims description 62
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 claims description 60
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims description 52
- 235000006708 antioxidants Nutrition 0.000 claims description 49
- 235000005911 diet Nutrition 0.000 claims description 47
- 239000004255 Butylated hydroxyanisole Substances 0.000 claims description 42
- 235000019282 butylated hydroxyanisole Nutrition 0.000 claims description 42
- XOAAWQZATWQOTB-UHFFFAOYSA-N taurine Chemical compound NCCS(O)(=O)=O XOAAWQZATWQOTB-UHFFFAOYSA-N 0.000 claims description 42
- 241000282414 Homo sapiens Species 0.000 claims description 40
- 230000000378 dietary effect Effects 0.000 claims description 40
- 239000004322 Butylated hydroxytoluene Substances 0.000 claims description 39
- 235000010354 butylated hydroxytoluene Nutrition 0.000 claims description 39
- ALYNCZNDIQEVRV-UHFFFAOYSA-N 4-aminobenzoic acid Chemical compound NC1=CC=C(C(O)=O)C=C1 ALYNCZNDIQEVRV-UHFFFAOYSA-N 0.000 claims description 38
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 38
- 102000019197 Superoxide Dismutase Human genes 0.000 claims description 37
- 108010012715 Superoxide dismutase Proteins 0.000 claims description 37
- LXNHXLLTXMVWPM-UHFFFAOYSA-N pyridoxine Chemical compound CC1=NC=C(CO)C(CO)=C1O LXNHXLLTXMVWPM-UHFFFAOYSA-N 0.000 claims description 37
- 201000011510 cancer Diseases 0.000 claims description 36
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 claims description 34
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 claims description 33
- 229940024606 amino acid Drugs 0.000 claims description 32
- 235000001014 amino acid Nutrition 0.000 claims description 32
- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 claims description 32
- 229940029985 mineral supplement Drugs 0.000 claims description 31
- 235000020786 mineral supplement Nutrition 0.000 claims description 31
- 235000020772 multivitamin supplement Nutrition 0.000 claims description 31
- 235000010388 propyl gallate Nutrition 0.000 claims description 31
- 239000000473 propyl gallate Substances 0.000 claims description 31
- 229940075579 propyl gallate Drugs 0.000 claims description 31
- OENHQHLEOONYIE-JLTXGRSLSA-N β-Carotene Chemical compound CC=1CCCC(C)(C)C=1\C=C\C(\C)=C\C=C\C(\C)=C\C=C\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C OENHQHLEOONYIE-JLTXGRSLSA-N 0.000 claims description 31
- 239000011669 selenium Substances 0.000 claims description 30
- 229910052711 selenium Inorganic materials 0.000 claims description 30
- 235000011649 selenium Nutrition 0.000 claims description 30
- 229940091258 selenium supplement Drugs 0.000 claims description 30
- 235000019165 vitamin E Nutrition 0.000 claims description 30
- 239000011709 vitamin E Substances 0.000 claims description 30
- AUNGANRZJHBGPY-SCRDCRAPSA-N Riboflavin Chemical compound OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-SCRDCRAPSA-N 0.000 claims description 29
- BUGBHKTXTAQXES-UHFFFAOYSA-N Selenium Chemical compound [Se] BUGBHKTXTAQXES-UHFFFAOYSA-N 0.000 claims description 29
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 claims description 29
- 235000010234 sodium benzoate Nutrition 0.000 claims description 29
- 239000004299 sodium benzoate Substances 0.000 claims description 29
- 229930003427 Vitamin E Natural products 0.000 claims description 28
- 235000013734 beta-carotene Nutrition 0.000 claims description 28
- 239000011648 beta-carotene Substances 0.000 claims description 28
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 claims description 28
- 229940046009 vitamin E Drugs 0.000 claims description 28
- OENHQHLEOONYIE-UKMVMLAPSA-N all-trans beta-carotene Natural products CC=1CCCC(C)(C)C=1/C=C/C(/C)=C/C=C/C(/C)=C/C=C/C=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C OENHQHLEOONYIE-UKMVMLAPSA-N 0.000 claims description 27
- TUPZEYHYWIEDIH-WAIFQNFQSA-N beta-carotene Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1=C(C)CCCC1(C)C)C=CC=C(/C)C=CC2=CCCCC2(C)C TUPZEYHYWIEDIH-WAIFQNFQSA-N 0.000 claims description 27
- 229960002747 betacarotene Drugs 0.000 claims description 27
- FPIPGXGPPPQFEQ-OVSJKPMPSA-N all-trans-retinol Chemical compound OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-OVSJKPMPSA-N 0.000 claims description 26
- 229910052804 chromium Inorganic materials 0.000 claims description 26
- 239000011651 chromium Substances 0.000 claims description 26
- 235000019155 vitamin A Nutrition 0.000 claims description 26
- 239000011719 vitamin A Substances 0.000 claims description 26
- FPIPGXGPPPQFEQ-UHFFFAOYSA-N 13-cis retinol Natural products OCC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-UHFFFAOYSA-N 0.000 claims description 25
- VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 claims description 25
- QYSXJUFSXHHAJI-XFEUOLMDSA-N Vitamin D3 Natural products C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C/C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-XFEUOLMDSA-N 0.000 claims description 25
- 239000011575 calcium Substances 0.000 claims description 25
- FPIPGXGPPPQFEQ-BOOMUCAASA-N Vitamin A Natural products OC/C=C(/C)\C=C\C=C(\C)/C=C/C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-BOOMUCAASA-N 0.000 claims description 24
- 229940045997 vitamin a Drugs 0.000 claims description 24
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 23
- 229910052700 potassium Inorganic materials 0.000 claims description 23
- 229960002477 riboflavin Drugs 0.000 claims description 23
- 239000007939 sustained release tablet Substances 0.000 claims description 23
- QYSXJUFSXHHAJI-YRZJJWOYSA-N vitamin D3 Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C\C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-YRZJJWOYSA-N 0.000 claims description 23
- 235000005282 vitamin D3 Nutrition 0.000 claims description 23
- 239000011647 vitamin D3 Substances 0.000 claims description 23
- 229940021056 vitamin d3 Drugs 0.000 claims description 23
- AUNGANRZJHBGPY-UHFFFAOYSA-N D-Lyxoflavin Natural products OCC(O)C(O)C(O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-UHFFFAOYSA-N 0.000 claims description 22
- 239000011591 potassium Substances 0.000 claims description 22
- 235000007686 potassium Nutrition 0.000 claims description 22
- 229910052710 silicon Inorganic materials 0.000 claims description 22
- 239000010703 silicon Substances 0.000 claims description 22
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 21
- 102000016938 Catalase Human genes 0.000 claims description 21
- 108010053835 Catalase Proteins 0.000 claims description 21
- DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 claims description 21
- 235000001465 calcium Nutrition 0.000 claims description 21
- 229910052791 calcium Inorganic materials 0.000 claims description 21
- 235000013305 food Nutrition 0.000 claims description 21
- 229960003966 nicotinamide Drugs 0.000 claims description 21
- 235000005152 nicotinamide Nutrition 0.000 claims description 21
- 239000011570 nicotinamide Substances 0.000 claims description 21
- 229960003080 taurine Drugs 0.000 claims description 21
- 229910052720 vanadium Inorganic materials 0.000 claims description 21
- 229910052742 iron Inorganic materials 0.000 claims description 20
- 229910052750 molybdenum Inorganic materials 0.000 claims description 20
- 239000011733 molybdenum Substances 0.000 claims description 20
- LEONUFNNVUYDNQ-UHFFFAOYSA-N vanadium atom Chemical compound [V] LEONUFNNVUYDNQ-UHFFFAOYSA-N 0.000 claims description 20
- ZOKXTWBITQBERF-UHFFFAOYSA-N Molybdenum Chemical compound [Mo] ZOKXTWBITQBERF-UHFFFAOYSA-N 0.000 claims description 19
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 claims description 19
- 229940011671 vitamin b6 Drugs 0.000 claims description 19
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 18
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 18
- 239000011777 magnesium Substances 0.000 claims description 18
- 235000001055 magnesium Nutrition 0.000 claims description 18
- 229910052749 magnesium Inorganic materials 0.000 claims description 18
- RADKZDMFGJYCBB-UHFFFAOYSA-N pyridoxal hydrochloride Natural products CC1=NC=C(CO)C(C=O)=C1O RADKZDMFGJYCBB-UHFFFAOYSA-N 0.000 claims description 18
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 claims description 17
- 229960002685 biotin Drugs 0.000 claims description 17
- 235000020958 biotin Nutrition 0.000 claims description 17
- 239000011616 biotin Substances 0.000 claims description 17
- 239000012141 concentrate Substances 0.000 claims description 17
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 claims description 17
- SHUZOJHMOBOZST-UHFFFAOYSA-N phylloquinone Natural products CC(C)CCCCC(C)CCC(C)CCCC(=CCC1=C(C)C(=O)c2ccccc2C1=O)C SHUZOJHMOBOZST-UHFFFAOYSA-N 0.000 claims description 17
- 239000011716 vitamin B2 Substances 0.000 claims description 17
- GHOKWGTUZJEAQD-ZETCQYMHSA-N (D)-(+)-Pantothenic acid Chemical compound OCC(C)(C)[C@@H](O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-ZETCQYMHSA-N 0.000 claims description 16
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 claims description 16
- OVBPIULPVIDEAO-UHFFFAOYSA-N N-Pteroyl-L-glutaminsaeure Natural products C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-UHFFFAOYSA-N 0.000 claims description 16
- 229930003471 Vitamin B2 Natural products 0.000 claims description 16
- 230000003078 antioxidant effect Effects 0.000 claims description 16
- 229910052796 boron Inorganic materials 0.000 claims description 16
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 claims description 16
- 229960000304 folic acid Drugs 0.000 claims description 16
- 235000019152 folic acid Nutrition 0.000 claims description 16
- 239000011724 folic acid Substances 0.000 claims description 16
- 229930182817 methionine Natural products 0.000 claims description 16
- 235000006109 methionine Nutrition 0.000 claims description 16
- 235000010199 sorbic acid Nutrition 0.000 claims description 16
- 239000004334 sorbic acid Substances 0.000 claims description 16
- 229940075582 sorbic acid Drugs 0.000 claims description 16
- 235000019164 vitamin B2 Nutrition 0.000 claims description 16
- 235000019154 vitamin C Nutrition 0.000 claims description 16
- 239000011718 vitamin C Substances 0.000 claims description 16
- ZAKOWWREFLAJOT-UHFFFAOYSA-N DL-alpha-tocopherylacetate Chemical compound CC(=O)OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C ZAKOWWREFLAJOT-UHFFFAOYSA-N 0.000 claims description 15
- SQUHHTBVTRBESD-UHFFFAOYSA-N Hexa-Ac-myo-Inositol Natural products CC(=O)OC1C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C1OC(C)=O SQUHHTBVTRBESD-UHFFFAOYSA-N 0.000 claims description 15
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 claims description 15
- 229960000367 inositol Drugs 0.000 claims description 15
- CDAISMWEOUEBRE-GPIVLXJGSA-N inositol Chemical compound O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](O)[C@@H]1O CDAISMWEOUEBRE-GPIVLXJGSA-N 0.000 claims description 15
- IKGXIBQEEMLURG-NVPNHPEKSA-N rutin Chemical compound O[C@@H]1[C@H](O)[C@@H](O)[C@H](C)O[C@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@H](OC=2C(C3=C(O)C=C(O)C=C3OC=2C=2C=C(O)C(O)=CC=2)=O)O1 IKGXIBQEEMLURG-NVPNHPEKSA-N 0.000 claims description 15
- CDAISMWEOUEBRE-UHFFFAOYSA-N scyllo-inosotol Natural products OC1C(O)C(O)C(O)C(O)C1O CDAISMWEOUEBRE-UHFFFAOYSA-N 0.000 claims description 15
- CHHHXKFHOYLYRE-UHFFFAOYSA-M 2,4-Hexadienoic acid, potassium salt (1:1), (2E,4E)- Chemical compound [K+].CC=CC=CC([O-])=O CHHHXKFHOYLYRE-UHFFFAOYSA-M 0.000 claims description 14
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 14
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 claims description 14
- 229930003268 Vitamin C Natural products 0.000 claims description 14
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 claims description 14
- 229960002433 cysteine Drugs 0.000 claims description 14
- 235000021323 fish oil Nutrition 0.000 claims description 14
- 239000011630 iodine Substances 0.000 claims description 14
- 229910052740 iodine Inorganic materials 0.000 claims description 14
- 235000019175 phylloquinone Nutrition 0.000 claims description 14
- 239000011772 phylloquinone Substances 0.000 claims description 14
- MBWXNTAXLNYFJB-NKFFZRIASA-N phylloquinone Chemical compound C1=CC=C2C(=O)C(C/C=C(C)/CCC[C@H](C)CCC[C@H](C)CCCC(C)C)=C(C)C(=O)C2=C1 MBWXNTAXLNYFJB-NKFFZRIASA-N 0.000 claims description 14
- 229960001898 phytomenadione Drugs 0.000 claims description 14
- 235000010241 potassium sorbate Nutrition 0.000 claims description 14
- 239000004302 potassium sorbate Substances 0.000 claims description 14
- 229940069338 potassium sorbate Drugs 0.000 claims description 14
- 235000019158 vitamin B6 Nutrition 0.000 claims description 14
- 239000011726 vitamin B6 Substances 0.000 claims description 14
- 239000011701 zinc Substances 0.000 claims description 14
- 229910052725 zinc Inorganic materials 0.000 claims description 14
- ABSPRNADVQNDOU-UHFFFAOYSA-N Menaquinone 1 Natural products C1=CC=C2C(=O)C(CC=C(C)C)=C(C)C(=O)C2=C1 ABSPRNADVQNDOU-UHFFFAOYSA-N 0.000 claims description 13
- 229930003779 Vitamin B12 Natural products 0.000 claims description 13
- 229960002743 glutamine Drugs 0.000 claims description 13
- 229910052748 manganese Inorganic materials 0.000 claims description 13
- 239000011572 manganese Substances 0.000 claims description 13
- 235000019163 vitamin B12 Nutrition 0.000 claims description 13
- 239000011715 vitamin B12 Substances 0.000 claims description 13
- 235000001809 DL-alpha-tocopherylacetate Nutrition 0.000 claims description 12
- 239000011626 DL-alpha-tocopherylacetate Substances 0.000 claims description 12
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 claims description 12
- PWHULOQIROXLJO-UHFFFAOYSA-N Manganese Chemical compound [Mn] PWHULOQIROXLJO-UHFFFAOYSA-N 0.000 claims description 12
- 235000010323 ascorbic acid Nutrition 0.000 claims description 12
- 239000011668 ascorbic acid Substances 0.000 claims description 12
- 235000018417 cysteine Nutrition 0.000 claims description 12
- 229960004452 methionine Drugs 0.000 claims description 12
- 229960003495 thiamine Drugs 0.000 claims description 12
- DPJRMOMPQZCRJU-UHFFFAOYSA-M thiamine hydrochloride Chemical compound Cl.[Cl-].CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N DPJRMOMPQZCRJU-UHFFFAOYSA-M 0.000 claims description 12
- XLOMVQKBTHCTTD-UHFFFAOYSA-N zinc oxide Inorganic materials [Zn]=O XLOMVQKBTHCTTD-UHFFFAOYSA-N 0.000 claims description 12
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 claims description 11
- 235000010376 calcium ascorbate Nutrition 0.000 claims description 11
- 239000011692 calcium ascorbate Substances 0.000 claims description 11
- 229940047036 calcium ascorbate Drugs 0.000 claims description 11
- BLORRZQTHNGFTI-ZZMNMWMASA-L calcium-L-ascorbate Chemical compound [Ca+2].OC[C@H](O)[C@H]1OC(=O)C(O)=C1[O-].OC[C@H](O)[C@H]1OC(=O)C(O)=C1[O-] BLORRZQTHNGFTI-ZZMNMWMASA-L 0.000 claims description 11
- 229940117373 dl-alpha tocopheryl acetate Drugs 0.000 claims description 11
- FFEARJCKVFRZRR-UHFFFAOYSA-N methionine Chemical compound CSCCC(N)C(O)=O FFEARJCKVFRZRR-UHFFFAOYSA-N 0.000 claims description 11
- 229960000342 retinol acetate Drugs 0.000 claims description 11
- 235000019173 retinyl acetate Nutrition 0.000 claims description 11
- 239000011770 retinyl acetate Substances 0.000 claims description 11
- QGNJRVVDBSJHIZ-QHLGVNSISA-N retinyl acetate Chemical compound CC(=O)OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C QGNJRVVDBSJHIZ-QHLGVNSISA-N 0.000 claims description 11
- PMYDPQQPEAYXKD-UHFFFAOYSA-N 3-hydroxy-n-naphthalen-2-ylnaphthalene-2-carboxamide Chemical compound C1=CC=CC2=CC(NC(=O)C3=CC4=CC=CC=C4C=C3O)=CC=C21 PMYDPQQPEAYXKD-UHFFFAOYSA-N 0.000 claims description 10
- QPLDLSVMHZLSFG-UHFFFAOYSA-N Copper oxide Chemical compound [Cu]=O QPLDLSVMHZLSFG-UHFFFAOYSA-N 0.000 claims description 10
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 claims description 10
- 229960002079 calcium pantothenate Drugs 0.000 claims description 10
- 235000019161 pantothenic acid Nutrition 0.000 claims description 10
- 239000011713 pantothenic acid Substances 0.000 claims description 10
- 235000018716 sodium selenate Nutrition 0.000 claims description 10
- 239000011655 sodium selenate Substances 0.000 claims description 10
- 229960001881 sodium selenate Drugs 0.000 claims description 10
- FAPWYRCQGJNNSJ-UBKPKTQASA-L calcium D-pantothenic acid Chemical compound [Ca+2].OCC(C)(C)[C@@H](O)C(=O)NCCC([O-])=O.OCC(C)(C)[C@@H](O)C(=O)NCCC([O-])=O FAPWYRCQGJNNSJ-UBKPKTQASA-L 0.000 claims description 9
- 150000003839 salts Chemical class 0.000 claims description 9
- 235000015393 sodium molybdate Nutrition 0.000 claims description 9
- 239000011684 sodium molybdate Substances 0.000 claims description 9
- TVXXNOYZHKPKGW-UHFFFAOYSA-N sodium molybdate (anhydrous) Chemical compound [Na+].[Na+].[O-][Mo]([O-])(=O)=O TVXXNOYZHKPKGW-UHFFFAOYSA-N 0.000 claims description 9
- IFQSXNOEEPCSLW-DKWTVANSSA-N L-cysteine hydrochloride Chemical compound Cl.SC[C@H](N)C(O)=O IFQSXNOEEPCSLW-DKWTVANSSA-N 0.000 claims description 8
- 239000001506 calcium phosphate Substances 0.000 claims description 8
- QSWDMMVNRMROPK-UHFFFAOYSA-K chromium(3+) trichloride Chemical compound [Cl-].[Cl-].[Cl-].[Cr+3] QSWDMMVNRMROPK-UHFFFAOYSA-K 0.000 claims description 8
- GHOKWGTUZJEAQD-UHFFFAOYSA-N Chick antidermatitis factor Natural products OCC(C)(C)C(O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-UHFFFAOYSA-N 0.000 claims description 7
- 239000004115 Sodium Silicate Substances 0.000 claims description 7
- 229940093797 bioflavonoids Drugs 0.000 claims description 7
- 239000000395 magnesium oxide Substances 0.000 claims description 7
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- POEVDIARYKIEGF-CEOVSRFSSA-L zinc;(2s)-2-aminobutanedioate;hydron Chemical compound [Zn+2].[O-]C(=O)[C@@H](N)CC(O)=O.[O-]C(=O)[C@@H](N)CC(O)=O POEVDIARYKIEGF-CEOVSRFSSA-L 0.000 description 1
- HJSYJHHRQVHHMQ-TYYBGVCCSA-L zinc;(e)-but-2-enedioate Chemical compound [Zn+2].[O-]C(=O)\C=C\C([O-])=O HJSYJHHRQVHHMQ-TYYBGVCCSA-L 0.000 description 1
- UOXSXMSTSYWNMH-UHFFFAOYSA-L zinc;2-aminoacetate Chemical compound [Zn+2].NCC([O-])=O.NCC([O-])=O UOXSXMSTSYWNMH-UHFFFAOYSA-L 0.000 description 1
- XLMCDAMBOROREP-UHFFFAOYSA-N zinc;3-phosphonooxypropane-1,2-diolate Chemical compound [Zn+2].OP(O)(=O)OCC([O-])C[O-] XLMCDAMBOROREP-UHFFFAOYSA-N 0.000 description 1
- AGFGXVAAIXIOFZ-UHFFFAOYSA-L zinc;butanedioate Chemical compound [Zn+2].[O-]C(=O)CCC([O-])=O AGFGXVAAIXIOFZ-UHFFFAOYSA-L 0.000 description 1
- JDLYKQWJXAQNNS-UHFFFAOYSA-L zinc;dibenzoate Chemical compound [Zn+2].[O-]C(=O)C1=CC=CC=C1.[O-]C(=O)C1=CC=CC=C1 JDLYKQWJXAQNNS-UHFFFAOYSA-L 0.000 description 1
- RNZCSKGULNFAMC-UHFFFAOYSA-L zinc;hydrogen sulfate;hydroxide Chemical compound O.[Zn+2].[O-]S([O-])(=O)=O RNZCSKGULNFAMC-UHFFFAOYSA-L 0.000 description 1
- CHJMFFKHPHCQIJ-UHFFFAOYSA-L zinc;octanoate Chemical compound [Zn+2].CCCCCCCC([O-])=O.CCCCCCCC([O-])=O CHJMFFKHPHCQIJ-UHFFFAOYSA-L 0.000 description 1
- NHVUUBRKFZWXRN-UHFFFAOYSA-L zinc;pyridine-2-carboxylate Chemical compound C=1C=CC=NC=1C(=O)O[Zn]OC(=O)C1=CC=CC=N1 NHVUUBRKFZWXRN-UHFFFAOYSA-L 0.000 description 1
- PEUPCBAALXHYHP-UHFFFAOYSA-L zinc;selenite Chemical compound [Zn+2].[O-][Se]([O-])=O PEUPCBAALXHYHP-UHFFFAOYSA-L 0.000 description 1
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- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
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Abstract
2074527 9111117 PCTABS00006 The present invention concerns a formulation of vitamins, minerals and other beneficial supplements. It is believed that the formulations of the present invention will not only extend longevity but also protect against diseases such as certain cancers and cardiovascular disorders as well as to facilitate immunological integrity in humans. More specifically, the invention is directed to a formulation and methods of manufacturing and administering a formulation containing vitamins and minerals in association with antioxidants, fish oils, enzymes, and amino acids. The formulations of the present invention provide synergistic relationships which have not previously been reported. As a preferred embodiment, the formulations of the present invention are manufactured as a sustained-release tableted dietary supplement and are intended as daily supplements.
Description
2~ 7 PCT/US91/00719 r TIME RELEASE FORM~LATION OF VITAMINS, MINERALS
Vitamins and minerals may be broadly defined as -substances that are essential for the maintenance of normal metabolic function but are not synthesized in the body.
These substances must be furnished from an exogenous source. A healthy individual ingesting a well-balanced diet receives adequate amounts of vitamins and minerals ;-from food. Vitamins obtained in this manner are not generally regarded as drugs.
However, there are many situations in which the concentration of one or more vitamins or minerals in the body tissues may be suboptimal. When such circumstances arise or can be anticipated, it is the common practice to administer vitamins or minerals in a chemically pure form.
When employed in this manner, vitamins and minerals may be regarded as drugs and a knowledge of their pharmacological properties is desirable. For example, large doses of various vitamins are frequently employed for the treatment of disorders that are not etiologically related to vitamin deficiency. The implication is that such large doses may exert pharmacodynamic actions that are useful in therapy.
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It should be noted, however, that excessive administration of certain vitamins, notably vitamin A, can cause untoward toxic effects.
In today's fast paced society many physicians and dieticians believe that a daily dietary vitamin and mineral : - ., .: , . ~...................... . . .
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2~7~ J~ - 2 -supplement acts prophylactically to prevent pathologies associated ~ith vitamin and mineral deficiencies. These supplements typically include several vitamins and minerals, and are referred to as multi-vitamin formulations. Examples of these preparations include One-A-Day~ and Centrum~ multi-vitamins. Researchers have suggested that multi-vitamins which include large quantities of vitamins and minerals are effective both for prophylactic purposes and for the treatment of an enormous variety of illnesses. Many millions of individuals living in the United States regularly ingest multi-vitamin preparations.
Some of these multi-vitamin preparations contain amounts of vitamins and minerals that are in excess of the RDA daily requirements. In the case of the water-soluble vitamins, there is little harm done to the body because of the low toxicity of this class of compounds. The low toxicity of the water-soluble vitamins is attributable to the fact that excess quantities of these substances are rapidly excreted in the urine. In the case of the lipid-soluble vitamins, the compounds accumulate in the body fat and can cause untoward toxic effects.
It is extremely important to distinguish between supplemental and therapeutic vitamin preparations. The latter contains much larger quantities of the individual vitamins and minerals than do the supplemental preparations. The present invention is directed to supplemental preparations.
The use of dietary multi-vitamin supplements should be considered by the physician in a wide variety of situations. Such situations may result from (l) inadequate vitamin intake, (2) mal-absorption syndromes, and (3) increased tissue requirements.
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Vitamin deficiency due to an inadequate intake arises in a variety of circumstances. There are still large parts of the world and even considerable areas in the United States where, owing to poverty, the population eats a diet inadequate in terms of vitamin content. Moreover, there are areas where the prevalence in the diet of one particular type of food results in a relatively high incidence of vitamin deficiencies. Eccentric diets resulting from psychiatric disturbance, individual idiosyncrasies, religious beliefs, or food fads are other major causes of vitamin deficiency. A decrease in food consumption because of excess use of alcoholic beverages, poor appetite, dieting to combat obesity, or restricted diets prescribed by physicians for the management of specific diseases represents a further group of situations in which vitamin deficiency can arise.
A disturbance in absorption of vitamins is also seen in a variety of conditions. Examples are diseases of the liver and biliary tract, prolonged diarrhea from any cause, hyperthyroidism, pernicious anemia, and a variety of other disorders of the digestive system. Moreover, since a substantial proportion of certain vitamins is provided by the bacteria of the gastrointestinal tract, treatment with antimicrobials that alter the intestinal bacterial flora may lead inevitably to a decreased vitamin absorption.
Increased tissue requirements for vitamins also occur under a variety of conditions so that a nutritional defi-ciency may develop on a diet that had previously been adeguate. Such situations can occur in both health and disease. In healthy individuals, for example, there is a greater requirement for various nutrients, including vita-mins, during growth, during periods of hard physical work, exercise, during pregnancy, lactation, and menstruation.
Diseases associated with an increased metabolism, such as hyperthyroidism, and conditions accompanied by fever or ..
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2~ 7 - 4 tissue wasting also increase the body~s requirements for vitamins. There is also good evidence that vitamin requirements increase during stress and after injury.
Multiple-vitamin therapy, using supplemental dietary multi-vitamins, is desirable in a variety of situations.
Since deficiency of a single vitamin is rarely encountered clinically, it is customary practice in cases of suspected vitamin deficiency, as well as in prophylactic treatment, to recommend that multiple-vitamin therapy be administered.
Typical of the multi-vitamins available are One-A-Day and Centrum multi-vitamins. (Table 1). Multi-vitamins such as these provide a great number of the essential vitamins and minerals needed by healthy individuals. Further, these preparations include electrolytes, and trace elements.
Recently, it has been determined that antioxidants, and free radical scavenging agents are protective against the development of certain cancers. Although, multi-vitamin preparations currently available include many needed vita-mins and minerals, they do not include the antioxidants and/or free radical scavengers which have been shown to enhance the immune system and to prevent certain cancers, cardiovascular disorders, inflammatory diseases and to slow ageing. Further, currently available multi-vitamin preparations do not include cardio-protective inositol or Omega-3 fish oils. Still further, several enzymes, amino acids, and dietary supplements which are known to be neces-sary and beneficial in supplementing an individual's diet are not included in presently available multi-vitamins.
Accordingly, a new multi-vitamin dietary supplement is needed which incorporates many of these beneficial ingredi-ents into a stable pharmaceutical preparation.
The present invention concerns development of a multi-vitamin dietary supplement formulation which includes several dietary supplements which are cardio- and cancer-protective as well as immunostimulatory. By including ,' ' . '.i................................ . ............. ...
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these cardio- and cancer-protective immunostimulatory compounds into a multi-vitamin formulation, the present invention advantageously provides the general population the benefits of recent scientific research which has S discovered that several agents are, for example, cardio-and cancer-protective. Accordingly, it is believed that the inventive methods and formulations will provide the general population with an improved multi-vitamin formulation capable of reducing the incidence of diseases such as heart disease and cancer while enhancing longevity and the immune system.
The present invention is directed to a formulation including vitamins, minerals and other beneficial supplements. More specifically, the invention is directed to a formulation and methods of manufacturing an*
administering a formulation containing vitamins and minerals in association with antioxidants, fish oils, food concentrate containing naturally occurring anti-oxidizing enzymes such as catalase and superoxide dismutase, for example, and amino acids. The formulations of the present invention exploit synergistic relationships which have not previously been reported.
One aspect of the present invention is directed to a multi-vitamin and mineral supplement which includes at least one antioxidant selected from the group consisting of BHT, BHA, propyl gallate, and sodium benzoate.
Several of the antioxidants, vitamins and minerals contained in the formulation have been shown to inhibit the induction of cancer at several stages in the multistage process. For example, B-carotene, glutathione, cysteine, 8HA, BHT, Vitamins A, C and E, as well as selenium, inhibit the tumor initiation, promotion and progression stages of cancer. The synergistic effects of BHA and Vitamin E, for example, are related to the observations that BHA inhibits :. , .~ . ............. . , .- ,: ~ , .
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W091/11117 PCT/US91tO0719 ~ ~?
2~7 ~ ;7 - 6 -tumor promoter-induced polyamine synthesis, and Vitamin E
inhibits promoter-induced hyperplasia, thus leading to a synergistic effect. Furthermore, Vitamins A, C and E, selenium, BHA, BHT, and propyl gallate have been shown to inhibit tumor initiation by counteracting the covalent binding of carcinogen to DNA and the mutagenic effect of carcinogens.
A further aspect of the present invention is directed to a multi-vitamin and mineral supplement including antioxidants in combination with certain preferred amino acids selected from the group consisting of glutathione, cysteine, methionine, glutamine, and taurine. According to a preferred embodiment, the inventive formulation further includes at least one of the following beneficial ingredients: omega-3 fish oil, para-aminobenzoic acid,;
superoxide dismutase, catalase (these two enzymes being preferably in food concentrates), bioflavonoids, and inositol.
-Preferably, the supplement of the present invention includes (but is not limited to) the following vitamins and minerals in an amount equal to or greater than the minimum daily requirement in man: vitamin C, folic acid, vitamin Bl, vitamin B2, niacinamide, vitamin B6, vitamin Bl2, vitamin D3, biotin, pantothenic acid, vitamin Kl, calcium, iodine, potassium, iron, magnesium, copper, zinc, manganese, chromium, molybdenum, selenium, vanadium, silicon, and boron.
An important aspect of the present invention is directed to a method for preventing cancer and cardiovascular disorders as well as increasing longevity and augmenting the immune system in a human subject. The method including the step of administering daily an oral sustained release tablet including the dietary multi-.
WO91/11117 2~ ~5~7 PCT/US91/00719 . ~,. ' ' ' ~ --' t - 7 - ~-vitamin and mineral supplement including antioxidants and other beneficial substances of the present invention.
! ~ ' A still further aspect of the present invention is directed to the production of a sustained-release tableted dietary supplement which is intended to be administered one to three times daily.
FIG. l graphically represents, as a function of %
potassium released versus time, the dissolution of Centrum tablets in gastric juice. ;
FIG. 2 graphically represents, as a function of %
potassium released versus time, the dissolution of the sustained release tablets of the present invention in intestinal juice.
FIG. 3 graphically represents, as a function of %
ascorbic acid released versus time, the dissolution of the sustained release tablets of the present invention in intestinal juice.
: .
FIG. 4 graphically represents, as a function of %
niacinamide released versus time, the dissolution of the sustained release tablets of the present invention in intestinal juice.
~, FIG. 5 graphically represents, as a function of pyridoxine % released versus time, the dissolution of the sustained release tablets of the present invention in intestinal juice.
The present invention concerns a formulation of vita-mins, minerals and other beneficial supplements. It is believed that the formulations of the present invention will not only extend longevity but also protect against certain cancers, immunological disorders and cardiovascular , WO91/11117 ~ PCT/US91/00719 2~ 8 disorders in humans. Generally, the invention is directed to a formulation and methods of manufacturing and administering a formulation containing vitamins and minerals in association with antioxidants, fish oils, anti-oxidizing enzymes preferably contained in food concentrates, and amino acids. It is believed that the formulations of the present invention will be beneficial in treating or preventing several pathologies, including various vitamin deficiencies, certain cancers, immunological disorders, and cardiovascular disease.
The formulations of the present invention exploit some synergistic relationships which have not previously been reported. The formulations of the present invention are particularly well adapted as a daily dietary supplement.
The present invention further involves a method for administering the formulations of the present invention to a person in need thereof. The preparation of the present formulations is also a component of the present invention.
Table l shows the anti-cancer effects of various components of the present formulation, individually and in synergistic combination.
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Table 1 Effects of antioxidant~ on 8kin Tumor Promotion-Antioxidant Tumor Response (mg) (% Inhibition) Control (DMBA + TPA) o BHA (0.5) 35 BHT (0.5) 32 Propyl gallate (0.5) 40 Vitamin E (0.1) 25 Vitamin C (0.5) 30 B-carotene (0.5) 20 Selenium (0.004) 23 BHA (0.5) + BHT (0.5) 92 BHA (0.5) + Vit E (0.1) 86 BHA (0.5) + Vit C (0.5) 98 Vit E (0.1) + Selenium (0.004) 94 Vit E (0.1) + B-carotene (0.5) 94 BHA (0.5) + B-carotene (0.5) 87 -BHA(O.l)+BHT(O.l)+Vit E(O.l)+B-carotene(0.1) 97 ^30 female mice (SENCAR) per group were used. The mice were initiated with 10 nmoles of 7,12-dimethylbenzanthracene and promoted with 1 ug of TPA 2x/~k. The antioxidants were applied simultaneously with TPA for the duration of experiment (30 weeks).
Table 2 illustrates the effects of certain antioxidant components of the present formulation on all the known spontaneous tumor formations and longevity in mice.
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2~ o -~able 2 Effects of Antioxidants on Aging and ~pontaneou~ Tumor Formation in ~ice- -Antioxidantsb Spontaneous Tumor Formation Increase in (% of Control) Lifespan (%~
Normal Diet lOO
Propyl gallate 62 127 ~100 mice (SENCAR) (50 males and 50 females) were used for each group. The groups receiving the antioxidants had them introduced in the normal laboratory chow (Wayne Research Animal Diet) at 0.5%.
Core ingredients in the most preferred formulation of the present invention are antioxidants and/or free radical scavenging agents of different types which protect against many kinds of free radicals and unstable molecules. In some cases, they work synergistically with other antioxidants, vitamins, and minerals. The following are the Core ingredients:
bioflavonoids L-glutathione (reduced) L-Cysteine Potassium sorbate/sorbic acid BHA
BHT
Propyl gallate Sodium benzoate Taurine D L-Methionine L-glutamine SOD and Catalase (preferably contained in food concentrate) ::.`: - - -- : :. 7 : :~ - ,: . . ..
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The significance and content of the Core ingredients may be described as follows: -- ' ~':
Bioflavonoids are ~iologically active compounds that have been shown to act as antioxidants, protecting vitamin C and other components from oxidation. certain bioflavonoids have been shown to have a protective effect against some cancers. The dosage of the bioflavonoid included is from about 2 to 200 mg, more preferably, from about 25 to about 150 mg, and most preferably, about 50 mg.
Preferable sources of bioflavonoid include citrus ;
bioflavonoid, vitamin P, vitamin P complex, rutin, orange peel bioflavonoid, grapefruit peel bioflavonoid, lemon bioflavonoid, lime bioflavonoid, flavonoids, kaempferol, narigenin, apigenin, naringin, naringenis, myricetin, delphinidin, quercetin, phloretin, cyanic, catechin, morin, phloridzin, phloretin, 3-hydroxyflavones, 3-deoxyflavonols, isorhamnetin, luteolin, tricin, chrysoeriol, hesperitin, eriodictyon, techtrochrysin, silybin, taxifolin, pinocembrim, galangin, robinin, diosmetin, kaempferide, fisetin, rhamnetin, and 3-0-methyl catechin. The most preferable source is, however, citrus bioflavonoid.
It is believed that glutathione may protect normal cells against radiation, free radicals and other toxic materials, and certain cancers. Functionally, glutathione is the proton donor used by glutathione peroxidase to remove free -radicals. Forms of glutathione useful in the practice of the present invention include: L-glutathione, S-ethylglutathione, S-butylglutathione, S-decylglutathione, S-heptylglutathione, S-methylglutathione, S-propylglutathione, S-pentylglutathione, S-octylglutathione and S-nonylglutathione. However, most preferably, glutathione is included in the formulations of the present invention as reduced L-glutathione. The dosage of glutathione included to the inventive formulation is .. ", ., ~, ~, ., . , . . . , - , . .
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WO91/11117 PCT/US91/0071~ ~
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2~7 A ~ l2 -preferably from about l to about 29 mg, and most - preferably, about lO mg.
L~Cysteine is an amino acid which has antioxidant propertieC and plays an important role in glutathione peroxidase activity. Cysteine also appears to have certain anticancer activity. Preferably, cysteine is included in the present invention as L-cysteine HCl, L-cysteine, L-acetyl cysteine, L-cysteine ethylester monohydrochloride, DL-cysteine, DL-cysteine HCl, L-cysteine methylester.
However, it is most preferred, that cysteine is included as L-cysteine HCl, in a dosage of from about 5 to about lOo mg, and more preferably, about 50 mg.
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Potassium sorbate and/or Sorbic acid are useful as a mold and yeast prohibitor. Sorbic acid has been shown to increase the effectiveness of antioxidant mixtures by acting synergistically with them. The sorbic acid dosage is preferably from about lO to 500 mg as potassium sorbate, sorbic acid, or sodium sorbate. Most preferably, however, the dosage of sorbic acid is about 200 mg as potassium sorbate.
In one important aspect of the present invention, the formulation includes at least one antioxidant. The antioxidant is preferably selected from the group consisting of butylated hydroxyanisole, butylated hydroxytoluene, propyl gallate, and sodium benzoate. The inventive formulation may include one, or, more preferably, several of the preferred antioxidants in combination.
According to one embodiment, the inventive formulation includes butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), sodium benzoate, and propyl gallate.
Sodium benzoate, BHA, BHT and propyl gallate are all antioxidants used to -stabili~e cosmeticj pharmaceutical, and food products. It has been reported that these agents protect normal cells against radiation, free radicals, .. .'- . . ', : ,' ' ~ :': ' .,., ~' ' . , ' ' WO91/11117 ~ PCT/US91/00719 - 13 - ~ .
toxic chemicals and chemical carcinogens. It has also beën reported that these agents are protective against the induction of cancer by many cancer-causing agents in almost every tissue of the body. Further, the preferred antioxidants of the present invention have been reported to protect against cardiovascular disorders, enhance immune function and increase longevity. The preferred antioxidants of the present invention work synergistically with several vitamins, minerals, amino acids, enzymes, and other antioxidants or free radial scavengers included in the formulation of the present invention as will be described in detail below.
According to one embodiment, BHA is included in a daily dietary multi-vitamin and mineral formulation for humans administered on a 1-3 times daily basis. Preferably, from about l to amount 300 mg of BHA is included in combination with a number of vitamins and minerals. More preferably, however, the formulation includes from about lO to about 150 mq of BHA, and most preferably, about 50 mg of BHA.
BHA may be included in the inventive formulation as butylated hydroxyanisole, 3-tert-butyl-4-hydroxyanisole, or 2-tert-butyl-4-hydroxyanisole, but most preferably is butylated hydroxyanisole.
According to another preferred embodiment, BHT is included in a daily dietary multi-vitamin and mineral formulation. Preferably, from about l to amount 300 mg of BHT is included in combination with a number of vitamins and minerals. More preferably, however, the formulation includes from about lO to about 150 mg of BHT, and most preferably, about 50 mg of BHT.
According to further embodiment, propyl gallate is included in the daily dietary multi-vitamin and mineral formulation. Preferably, from about l to amount 300 mg of propyl gallate is included in combination with a number of WO91/11117 PCT/~S91/~0719 2~7 ~ P~
vitamins and minerals. More preferably, however, the formulation includes from about lO to about 150 mg of propyl gallate, and most preferably, about 50 mg of propyl gallate.
Sodium benzoate, an antioxidant used to stabilize food and pharmaceutical products, according to another embodiment, is included in a d~ily dietary multi-vitamin and mineral formulation. Preferably, from about l to amount 300 mg of sodium benzoate is included in combination with a number of vitamins and minerals. More preferably, however, the formulation includes from about l to about 150 mg of sodium benzoate, and most preferably, about 4 mg of sodium benzoate. As described above, one embodiment of the inventive formulation includes sodium benzoate. However, it has been determined that potassium benzoate, benzoic acid, calcium benzoate, cuprous benzoate, cupric benzoate, manganese benzoate, nickel benzoate, magnesium benzoate are all also useful in the practice of the present invention.
2C Taurine is an amino acid used by the liver for conjugation with bile acids. It has also been suggested that taurine strengthens and stabilizes cellular membranes.
High concentrations of taurine are found in the brain.
Taurine, it is believed, acts in concert with the preferred antioxidants of the present invention to provide increased protection against cancer and certain cardiovascular diseases. Preferably, taurine is included in the formulations of the present invention in a dosage of from about l to about 20 mg, and most preferably, about lO mg.
Methionine is an essential amino acid which has antioxi-dant properties. Methionine is the principal source of methyl groups which are, in turn, transferred to many diverse acceptors in important physiological reactions, such as, methyl transferases. Methionine is preferably include in the formulations of the present invention as DL-methionine, L-methionine, S-adenosylmethionine, N-acetyl-.. ~ - .
WO91/11117 2f~ 5~ 7 PCT/US91/00719 ~.
methionine, S-methyl-DL-methionine-sulfonium chloride.
However, more preferably, methionine is included as DL-methionine, in a dosage of from about l to about 20 mg, and most preferably, about l0 mg.
Glutamine is an amino acid which serves as an amino donor in many reactions. Glutamine is critical for the de novo synthesis of purine and pyrimidine nucleotides. These nucleotides are critical to normal cell function and replication. Preferably, glutamine is included in the formulations of the present invention as L-glutamine, DL-glutamine, or N-acetyl-L-glutamine. However, most preferably, glutamine is included as L-glutamine, in a dosage of from about l to about 20 mg, and most preferably, about l0 mg.
Superoxide dismutase (SOD) stabilizes the formulations of the present invention and is an antioxidant. SOD
prevents the formation of singles oxygen, hydroxyl radicals and other reactive oxygen species. It is believed that SOD
can protect against cancer, cardiovascular disorders and increase longevity. The dosage included of SOD (superoxide dismutase) is preferably from about 20 to about 500 units, more preferably, from about l00 to about 300, and most preferably about 150 units (i.u.) (McCord/Fridovich units).
Preferable sources of SOD for the formulation of the present invention include purified liver SOD, bovine SOD, intercellular SOD, bovi~e liver SOD, erthrocytic SOD, extracellular SOD, vegetable culture SOD, vegetable SOD, bovine lyophilized liver SOD, fractionated liver SOD, fractionated erythrocyte SOD, and bacterial SOD. The most preferable source of SOD is, however, vegetable SOD, particularly as a food concentrate.
.
Catalase also stabilizes the formulations of the present invention and compliments SOD. Catalase converts hydrogen peroxide into water and oxygen. It is believed that , 2~ J7 - l6 -catalase protects against diseases such as cancer and cardiovascular disorders as well as increasing longevity.
The dosage of catalase included is from about 5 mg to 500 units, more preferably, from about lOO to about 300 units, and most preferably, about 150 units (i.u.) (Baker Units).
Preferable sources of catalase include that purified from bovine liver, fractionated liver, bacteria, Aspergillus niger, and vegetables. The most preferable source is, however, vegetables, particularly as a food concentrate.
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The core antioxidants can also interact synergistically with the following components, vitamins and minerals which are antioxidants additionally included in the preferred formulation (Core II):
Vitamin A
B-carotene (beta-carotene~
Vitamin E
Ca Ascorbate Copper Zinc Manganese Selenium omega-3 fish oil inositol PABA
Due to their importance both in the prevention of cancer and cardiovascular disorders, omega-3 fatty acid, PABA and inositol are also an important part of the Core II
formulation.
The Core II ingredients may be described as follows:
Vitamin A is a fat soluble vitamin essential in cell differentiation, vision, immunity, healthy skin, hair, and mucous membranes. This vitamin is also necessary for proper reproduction, bone growth and development of teeth.
Deficiencies have been associated with a higher incidence of certain cancers. Vitamin A appears to work synergistically with several other vitamins, as well as minerals and antioxidants, to lower cancer rates and to WO91/11117 2~ PCTtUSg1/00719 increase longevity. The dose of vitamin A preferably included is from about 1,000 to 3,000 i.u., and more preferably, about 2,000 i.u. Preferably, the vitamin A
source included in the formulation is vitamin A acetate, vitamin A palmitate, retinol, and retinal. The source of vitamin A may be water soluble, fat soluble, or emulsified.
Most preferably, however, the vitamin A source is emulsified vitamin A acetate.
Beta carotene or, provitamin A is a precursor to vitamin A. Beta carotene must be converted by the body into active retinol-type vitamin A to be utilized. Beta carotene is also a potent antioxidant and may prevent certain types of cancer. Beta carotene appears to work synergistically with several vitamins, minerals and antioxidants to lower cancer rates and to increase longevity. Although Vitamin A and other retinoids have been shown to inhibit the induction of skin cancer in mice, an unexpected result has been the lack of an inhibitory activity by B-carotene (beta carotene) in the mouse skin carcinoqenesis system. However, if B-carotene is given with low doses of vitamin E, BHA or BHT, it very effectively enhances their activity in a synergistic manner. The dosage of beta carotene included is preferably from about 2,500 to 7,500 provitamin A units as water soluble beta carotene, or emulsified beta carotene, and most preferably 5,000 provitamin A units as emulsified beta carotene.
Vitamin E is a fat soluble vitamin which functions as an antioxidant protecting lipid membranes against oxidation.
Deficiencies in vitamin E can increase the tendency of blood to clot. Vitamin E appears to work synergistically with several vitamins, minerals, e.g., selenium, and antioxidants to lower cancer rates and to increase longevity. The dosage of vitamin E included is preferably from about 10 to 100 units as DL-alpha tocopheryl acetate, DL-alpha tocopheryl succinate, water soluble DL-alpha .... ,, - ... - . ..
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: . , ~ : : . , . -: ,. ' .. ,, : : , . , :~ :
-2~ 18 tocopheryl acetate or succinate, emulsified DL-alpha tocopheryl acetate, D-alpha tocopheryl acetate, D-alpha tocopheryl succinate, mixed tocopherols, emulsified D-alpha tocopheryl acetate, emulsified mixed D-tocopherols, water soluble D-alpha tocopheryl acetate, water soluble mixed D-tocopherols, D-alpha tocopherol, emulsified D-alpha tocopherol, water soluble D-alpha tocopherol, or alpha tocopheryl nicotinate. Most preferably, however, the dosage of vitamin E is about lO0 units as vitamin E, DL-alpha tocopheryl acetate.
Vitamin C is a water soluble essential vitamin. It is critical in producing and maintaining collagen, promotes healing of wounds, aids tooth and bone formation, and is important in producing hormones that regulate basal metabolic rate and body temperature. Vitamin C also acts as an antioxidant and may counteract nitrosamines formed in the intestinal tract, and, therefore, helps reduce the rates of certain kinds of cancers. Vitamin C appears to work synergistically with several other vitamins, as well as minerals and antioxidants, to lower cancer rates and to increase longevity. The dosage of vitamin C included is preferably from about lO to l,000 mg as ascorbic acid, or salts of ascorbic acid including calcium ascorbate, magnesium ascorbate, sodium ascorbate, potassium ascorbate, esterified ascorbic acid, ascorbyl palmitate. Most preferably, however, the dosage of vitamin C is about 250 mg as calcium ascorbate. -~
Copper is a trace mineral essential for the formation of red blood cells and the utilization of iron. It also functions in electron transport, connective tissue metabolism and the development of the nervous system. ~ ;~
Deficiencies have been linked to nervous system disorders, bone disorders (spontaneous fractures) and anemia. Copper may protect against certain types of cancers. Copper dosage is 0.2 to 20 mg as copper oxide, cupric acetate, - "
-- 1 9 -- ~ ~ ~
cupric butyrate, cupric subcarbonate, cupric chloride, cupric citrate, cupric formate, cupric gluconate, cupric glycinate, cupric hydroxide, cupric oxide, cupric stearate, cupric sulfate, cupric subsulfate, copper gluconate, copper amino acid chelate, copper salicylate, copper proteinate, cupric tyrosinate, copper glycerophosphate, and copper picolinate.
zinc is a trace mineral essential to cell multiplication, tissue regeneration and wound healing, sexual maturity, and proper growth. zinc is required for many enzymatic functions throughout the body, and also helps regulate the immune system and insulin metabolism.
Preferably, the dosage of zinc included is from about dosage 2 to about 30 mg as zinc oxide, zinc acetate, zinc benzoate, zinc caprylate, zinc carbonate, zinc chloride, zinc citrate, zinc formate, zinc lactate, zinc selenate, zinc stearate, zinc sulfate, zinc picolinate, zinc gluconate, zinc sulfate heptahydrate, zinc sulfate monohydrate, zinc succinate, æinc amino acid chelate, zinc proteinate, zinc fumarate, zinc aspartate, zinc ascorbate, and zinc glycerophosphate. Most preferably, however, the dosage of zinc is about 15 mg as zinc oxide.
Manganese is a trace mineral essential to enzyme systems involved in bone development, insulin production as well as other enzyme systems. It is also required for the synthesis of cartilage mucopolysaccharides. Preferably, the manganese dosage is from about 0.5 to about 5 mg as manganese gluconate, manganese acetate, manganese carbonate, manganese chloride, manganese dioxide, manganese hypophosphite, manganese iodide, manganese silicate, manganese sulfate, manganese picolinate, manganese glycerophosphate, manganese lactate, manganese amino acid chelate, manganese proteinate, manganese ascorbate, manganese aspartate, manganese citrate, manganese fumarate, . . : ~ . - .
.. . . .- - . ....................... . - .
. - , , . . , . - , .
-. - . . ~. - -Z~ 7 - 20 -and manganese glycinate. More preferably, the manganese dosage i~ about 2.5 mg as manganese gluconate.
Selenium helps maintain proper immune system function.
It is an essential component of glutathione peroxidase, and as an antioxidant helps protect cells from free radical damage and toxic effects of certain chemicals.
Deficiencies are linked with increased risk of various cancers, along with increased risk of stroke, angina and heart attack. Selenium appears to work synergistically with several vitamins, minerals and antioxidants to lower cancer rates and to increase longevity. Preferably, the dosage of selenium included is from about 2 mcg to about l00 mcg as sodium selenate, selenous acid, potassium selenate, selenium oxide, selenomethionine, selenium yeast, selenium vegetable culture, selenium amino acid chelate, selenium proteinate, selenium ascorbate, selenium aspartate, sodium selenite, sodium selenate, potassium selenite, selenocystine, magnesium potassium selenate, magnesium selenate, cupric selenate, cupric selenite, zinc selenate, zinc selenite, calcium selenate, calcium selenite, selenium picoli~ate, selenium glycinate, and selenium glycerophosphate. Nost preferably, however, the dosage of selenium is about 25 mcg as sodium selenate.
Omega-3 (EPA/DHA) are polyunsaturated fatty acids.
Increased dietary levels of polyunsaturated fatty acids reduces platelet aggregation and has been linked to a lower incidence of heart disease and cancer. Omega 3 fish oils, preferably having an EPA:DHA ratio of about 18:12, are included in the supplement of the present invention in a dosage of from about l0 to about l,000 mg, more preferably, however, the dosage is from about 50 to about 800 mg, and most preferably about 200 mg. The omega-3 fish oil is preferably included as microencapsulated omega-3 fish oils, Omega 3 fish oils, cod liver oil, salmon oil, microencapsulated salmon oil, emulsified cod liver oil, k 5 , ~7 ", ""~
emulsified salmon oil, eicosapentaenoic acid, docosahexenoic acid, emulsified eicosapentaenopic acid, emulsified docosahexaenoic acid, fish oil, EPA, max EPA
sardine oil, microencapsulated sardine oil, halibut oil, or microencapsulated halibut oil. Most preferably, however, the omega-3 fish oil is microencapsulated omega-3 fish oil.
Inositol plays a vital metabolic role at the cellular level. Inositol is a bipotropic agent and plays a role in membrane and lipoprotein function. Inositol is preferably included in a dosage of from 5 to about lOOmg, and most preferably, about 50 mg.
According to one embodiment, the daily dietary multi-vitamin and mineral supplement of the present invention further includes para-aminobenzoic acid (PABA) in combination with the preferred amino acids and antioxidants of the present invention. PABA is an essential coenzyme in the metabolism of proteins and in the formation of red blood cells. PABA works synergistically with pantothenic acid. It has been reported that PABA may provide some pro-tection against hypertension and certain cancers. PABA is preferably included in the formulations of the present invention as para-aminobenzoic acid, potassium para-aminobenzoate, sodium para-aminobenzoate, magnesium para-aminobenzoate, calcium para-aminobenzoate. Most preferably, however, PABA is included as the acid in a dosage of from about lO to about lOO mg, and most preferably, about 40 mg.
Also, the following vitamins and minerals (Core IIIj, although not unique, are necessary and important in this f~ormulation because of their role in normal growth and general bodily needs. Once vitamins have crossed the intestinal walls, many function as co-enzymes essential to all cells. Because they work synergistically, or as a team, it is better to administer them together. A similar : . . . .
.
~ ,.
synergism is known for many of the minerals. They are as follows:
Folic Acid Vitamin B1 l vitamin B2 Niacinamide .vitamin B6 Vitamin B12 Vitamin D3 Biotin Ca Pantothenate Vitamin K~
Calcium Iodine Potassium Iron Magnesium Chromium Molybdenum Vanadium Silicon Boron ~-;
Compositions of the Core III formulations may be described as follows.
Folic Acid is an essential water-soluble vitamin. It is necessary for the synthesis of RNA and DNA, and therefore, vital in cell growth and division. Folic acid is important in red blood cell maturation and in other metabolic processes. The dose of folic acid included is from about 40 to about l,2000 mcg as folic acid, and most preferably, about 400 mcg. ;-Vitamin B1 (thiamine) is an essential water-soluble vita-min. It is important in the metabolism of carbohydrates and critical for the transmission of high-frequency impulses in the central nervous system as well as maintaining the integrity of the central nervous system.
Preferably, the dosage of vitamin B1 included is from about l to about 2 mg as thiamine hydrochloride, thiamine ~-mononitrate, thiamine chloride naphthalene-l, 5-disulfonic acid salt, thiamine triphosphoriate salt, thiamine : . : . .; , . . : , ~ .
% ~ ~ ~r~ ~
triphosphate ester, thiamine phosphoric acid ester phosphate salt, thiamine phosphoric acid ester chloride, and thiamine disulfide. Mos preferably, however, the dosage of vitamin B~ is about l.50 mg as thiamine hydrochloride.
Vitamin B2 (riboflavin) is an essential water-soluble vitamin which is required for the repair and growth of tissues as well as DNA synthesis. Vitamin B2 assists in metabolizing nutrients, e.g., proteins, fats and carbohydrates, and therefore, is critical in the release of energy. Preferably, the dosage of vitamin B2 is from about from 170 mcg to about 2 mg as riboflavin, riboflavin tetrabutyrate, riboflavin 5' phosphate sodium, and riboflavin monodiethanolamine salt dihydrate. Most preferably, however, the dosage of vitamin B2 is about l.75 mg as riboflavin.
Niacinamide is critical in the production of energy.
Niacinamide is water-soluble, and is an essential constituent of coenzymes I and II that occur in a wide variety of enzyme systems involved in the anaerobic oxidation of carbohydrates. Niacinamide is necessary for DNA formation, and important for the integrity of the central nervous system. Preferably, the dosage of niacinamide included is from about lO to about 30 mg as niacinamide, and most preferably, about 20 mg.
Vitamin B6 is a term commonly used for a group of three vitamins: pyridoxine, pyridoxal and pyridoxamine. They are important in protein and amino acid metabolism and help to regulate blood glucose levels. These vitamins are needed to synthesize hemoglobin and are important in the proper function of the central nervous system. The dosage of vitamin 88 is preferably from about 200 mcg to about 3 mg as pyridoxine hydrochloride, pyridoxal 5-phosphate, calcium .. . ' ~ : .-, .' , : , .
~ :: -~, .
2~ 24 -pyridoxine 5-phosphate, pyridoxal. Most preferably, however, the dosage of vitamin B6 is about 2 mg.
Vitamin B12 is an essential water soluble vitamin. It is critical for- bone growth, the integrity of the central nerve tissue, normal blood formation, and cell replication and DNA synthesis. Vitamin B1z deficiencies are related to certain anemias. Vitamin B12 is useful especially in the prevention of pernicious anemia. Preferably the dosage of Vitamin B12 included is from about 2 to about lO00 mcg as cyanocobalamin, cobalamin, Co-methylcyanocobalamin, zinc-vitamin B~2 - tannate, resin bound vitamin B12, and coenzyme Vitamin D3 is an oil-soluble vitamin. Vitamin D3 aids both the absorption of calcium and phosphorus. The primary role of vitamin D3 is the mineralization of bones and teeth and the regulation of blood calcium levels. Vitamin D3 is critical for the growth and differentiation of several tissues, and, it is believed, reduces the rate of certain cancers. The dosage of vitamin D3 included is preferably from about 40 to about 4,000 units as vitamin D3, water dispersable vitamin D3, water-soluble vitamin D3, and emulsified vitamin D3. Most preferably, however, the dose of vitamin D3 is about 600 units. ~
Biotin is a water-soluble vitamin essential in metabol- -ism. It is a coenzyme in the synthesis of fatty acids and amino acids. The dosage of biotin is preferably from lO to lO0 mcg as biotin, and most preferably, about 30 mcg. -Calcium pantothenate is a source of pantothenic acid, a water-soluble vitamin. Pantothenic acid is involved with the metabolism of proteins, fats and carbohydrates in the form of exoenzyme A, and is involved in the synthesis of sterols, hormones, porphyrins and acetylcholine. The ... . . . . . .
:, ., : -, . . : .
::.. .. - . : . : : - . . , : , . : : .
WO91tlll17 PCT/US91/00719 2 ~
- 25 - ; -dosage of calcium pantothenate is preferably from about 1 to about 50mg, and most preferably, about lOmg.
Vitamin K1 is an oil soluble vitamin which is necessary for the formation of prothrombinogen and other blood clotting factors. However, vitamin K-dependent protein in bone suggests a more complex role. Preferably, the dosage of Vitamin Kl is from about 3 to lOO mcg as trans isomer of vitamin K1, cis-trans isomers of vitamin Kl, emulsified trans isomer of vitamin K1, emulsified cis-trans isomers of vitamin K1, water soluble trans vitamin K1, water soluble cis-trans isomer of vitamin K1, vitamin K1 oxide, trans vitamin K1 oxide, emulsified cis-trans vitamin Kl oxide, water soluble trans vitamin Kl, water soluble cis-trans vitamin K1 oxide, vitamin K2 (2-methyl -3- all trans-polyprenyl-1, 4 napthoquinone) and those compounds of vitamin K2 which may possess side chains varying in length from C5 (n=1) to C6s (n=13), water soluble vitamin K2 and water soluble compounds of compounds of K2 which may possess side chains varying in length from C5 (n=1) to C65 (n=13), vitamin K5, dihydrovitamin K1, diphosphate ( ol, o4 diphosphoric acid) disodium salt of dihydrovitamin K1, tetrasodium salt of dihydrovitamin K1, tetrapotassium salt of dihydrovitamin K1, diphosphate ( ol, o4 - diphosphoric acid) dipotassium salt of dihydrovitamin K1, vitamin K6, vitamin K~, vitamin K~ hydrochloride, vitamin K5 (II), emulsified vitamin K5 (II), water soluble vitamin K5 (II).
Most preferably, however, the dose of vitamin K1 is about 25 mcg.
Calcium is involved with the transmission of nerve impulses, muscle contraction and relaxation, blood clotting, structure and function of cell membranes and B12 absorption. Dietary deficiencies are common and have been ~5 associated with accelerated bone loss resulting in alveolar bone loss and accompanying oral health problems, ",,~..... . - - - , , - . , .............. , , , , . , - . . . .
. : : .. ` . : : : - : -, ~:
. 2~ 26 -osteoporosis and hypertension. Calcium may also protect against certain type of cancer such as colon cancer Preferably, the calcium dosage included is from about 40 to about l,O00 mg as dicalcium phosphate dihydrate, dicalcium phosphate, monobasic calcium phosphate, tricalcium phosphate, calcium carbonate, calcium chloride, calcium citrate, calcium fluoride, calcium gluconate, calcium glycerophosphate, calcium hydroxide, calcium lactate, calcium levulinate, calcium sulfate, calcium succinate, calcium ascorbate, calcium fumarate, calcium lysinate, calcium malate, calcium aspartate, calcium amino acid chelate, calcium caseinate, calcium proteinate, calcium picolinate, calcium aspartate, calcium alpha ketoglutarate, calcium caseinate, calcium hydroxide, bone meal, oyster shell, calcium glycerophosphate, calcium hypophosphite, calcium ferrous citrate, calcium formate, calcium hypochlorite, calcium methionate, calcium biphosphate, calcium stearate, calcium tartrate, hydroxyapatite, dolomite, calcium sulfate dihydrate, calcium sulfate hemihydrate, dicalcium phosphate dihydrate, calcium acetate, calcium pyrophosphate, calcium gycinate. More preferable sources of calcium include calcium citrate, calcium carbonate, which act as free radical scavengers, calcium pantothenate, and dicalcium phosphate dihydrate.
Dicalcium phosphate dihydrate is source of calcium and phosphorus which functions in almost all aspects of metabolism, and also aids in the manufacturing (tableting) process.
Iodine is essential for proper thyroid functioning, and therefore, the regulation of the basal metabolic rate. The dosage of iodine included is from about 5 to 500 mcg as potassium iodide, sodium iodide, iodinated glycerol, kelp, Atlantic kelp, Pacific kelp, iodine-resublimed, potassium iodate, ferrous iodide, magnesium iodide, manganese iodide, iodine picolinate, iodine aspartate, iodine ,.. ,.. ~.. ,, ,., .. , , ~ - ................. , , ~ ,. . . .
.. . . . .. .
WO 9 1 /1 1 1 17 2~ - h5~ PCT/US9l/00719 2 7 ; . ` L . ' ' glycerophosphate. Most preferably, however, the dosage is about 150 mcg as potassium iodide.
Potassium is a major intracellular electrolyte.
Potassium aids in the transmission of nerve impulses, the release of insulin, and the proper functioning of digestive enzymes. Potassium works with sodium to maintain the balance of body fluids. Preferably, the dosage of 10 to about 1000 mg potassium is from about as potassium chloride, potassium acetate, potassium bicarbonate, potassium carbonate, potassium citrate, potassium gluconate, potassium glycerophosphate, potassium hydroxide, potassium nitrate, dipotassium phosphate, potassium dihydrogen phosphate, tripotassium phosphate, potassium sorbate, potassium sulfate, potassium proteinate, potassium amino acid chelate, potassium fumarate, potassium alpha ketoglutarate, potassium malate, potassium ascorbate, potassium succinate, potassium aspartate, potassium/magnesium aspartate, or potassium picolinate.
- Iron is an essential mineral and is needed to transport oxygen to the tissues throughout the body via hemoglobin and myoglobin. Iron is involved in the catalysis of many oxidative reactions within cells and is necessary for the proper functioning of many biochemical reactions. Iron plays a role in final steps of energy metabolism. Iron deficiencies are widespread, especially among women and children. Preferably, the dosage of iron included is from about 2 to about 50 mg as ferrous fumarate, ferrous carbonate mass, ferrous carbonate saccharated, ferrous chloride, ferrous citrate, ferrous gluconate, ferrous iodide, ferrous lactate, ferrous oxide, ferrous succinate, ferrous sulfate,- ferrous ascorbate, iron amino acid chelate, ferrous aspartate, ferrous peptonate, iron 3S proteinate, iron chloride, iron reduced, iron oxide saccharated, ferric glycerophosphate, and iron picolinate.
.. .
:.. ::: :
2~ ~,~7 - 28 -Most preferred, however, the dosage of iron is about 18 mg as iron gluconate.
Magnesium is a mineral essential for every biological S process including glucose metabolism, protein and nucleic acid synthesis, electrical balance of cells, and the trans-mission of nerve impulses. Magnesium effects the function and structure integrity and contractions of the heart and all other muscles. Dietary deficiencies are widespread.
Deficiencies have been linked to cardiovascular diseases.
Preferably, the dosage of magnesium included is from about 10 to about 500 mg as magnesium oxide, magnesium benzoate, magnesium carbonate hydroxide, magnesium chloride magnesium citrate, di-basic magnesium citrate, magnesium formate, magnesium hydroxide, magnesium iodide, magnesium lactate, magnesium peroxide, magnesium hydrogenphosphate, trimagnesium phosphate, magnesium silicate, magnesium stearate, magnesium sulfate, magnesium carbonate, magnesium gluconate, magnesium glycerophosphate, magnesium trisilicate, magnesium nicotinate, magnesium malate, magnesium amino acid chelate, magnesium picolinate, magnesium proteinate, magnesium lysinate, magnesium alpha ketoglutarate, and magnesium phosphinate hexahydrate. Most preferably, however, the dosage of magnesium is about 100 mg as magnesium oxide.
Chromium is a cofactor for insulin. Chromium is in-volved in carbohydrate metabolism, especially the utiliza-tion of glucose. Low chromium has been linked to diabetes and hypoglycemia. Low chromium has also been associated with heart disease. Chromium deficiencies are widespread.
Preferably, the dosage of chromium included is from about 2 to about 50 mcg as chromium ~+3) chloride, chromic acetate, chromic carbonate, chromic formate, chromic hydroxide, chromic nitrate, chromic oxide, chromic phosphate, chromic potassium sulfate, chromic sulfate, chromic picolinate, chromium polynicotinate, chromium ' ', ' . ' '`. . , ,, ' ' WO 91/11117 2~ PCT/US91/00719 ~ . r 2 9 ~ ~. . J.~
soured yeast, chromium vegetable culture, chromium amino - acid cheIated, chromium proteinate, chromium aspartate, chromium ascorbate, chromium GTF yeast, chromium glycinate, and chromium glycerophosphate. Most preferably, the dosage of chromium is about 25 mcg as chromium (+3) chloride.
Molybdenum is considered to be an essential trace mineral. Molybdenum plays a role in iron metabolism.
Preferably, the dosage of molybdenum included is from about 2 mcg to lO0 mcg as sodium molybdate, molybdenum amino acid chelate, molybdenum ascorbate, molybdenum yeast, molybdenum vegetable culture, molybdenum disulfide, molybdenum sesquioxide, molybdenum trioxide, sodium phosphomolybdate, molybdenum picolinate, molybdenum glycinate, and molybdenum glycerophosphate. Most preferably, however, the dosage of molybdenum is about 25 mcg as sodium molybdate.
Vanadium is a trace mineral found in the diet. Possible biochemical and physiological functions for vanadium have been suggested as including lipid metabolism, glucose metabolism, bone, and tooth metabolism. Vanadium may serve a catalytic function or may be an enzyme cofactor.
Preferably, the dosage of vanadium included is from about 2 mcg to about 100 mcg as sodium metavanadate, vanadium aspartate, vanadium amino acid chelate, vanadium proteinate, vanadium yeast, vanadium vegetable culture, potassium metavanadate, calcium vanadate, magnesium vanadate, ammonium metavanadate, vanadyl sulfate, oxytartarovanadate, vanadium picolinate, vanadium glycinate, and vanadium glycerophosphate.
.
Silicon functions as a biologic cross-linking agent that contributes to the structure and resilience of connective tissues, collagen, elastin and mucopolysaccharide. Silicon may be required for bone and cartilage collagen biosynthesis and is apparently involved in bone calcification. Preferably, the dosage of silicon included .,u.~...... , , , , ,, , ~ , , - , ~ , , ' -.. :
2~ ;.,7 is from about 2 mcg to about 50 mcg as sodium metasilicate, silica amino acid chelate, silicon proteinate, silicon plant source, silicon vegetable culture, silicon source trachea, silicon source tendon, silicon source aorta, silicon source mucopolysaccharide, silicon source pectin, silicon source alginic acid, silicic acid, silanolate, silicon dioxide, and silica. More preferably, the dosage of silicon is about 10 mcg as sodium metasilicate.
Findings suggest that boron influences the metabolism of calcium, phosphorus, magnesium and cholecalciferol. Boron may also be involved in the functional efficiency of membranes. Preferably, the dosage of boron included is from about dosage 500 mcg to about 2000 mcg as calcium borogluconate, magnesium borogluconate, sodium borate, boric acid, potassium borate, sodium metaborage, boron proteinate, boron amino acid chelate, glyceroborate, magnesium perborate, sodium perborate, calcium perborate, and potassium perborate. Most preferably, however, the dosage of boron is about 1 mg as calcium borogluconate.
With regard to the vitamins and minerals included in the inventive formulation, each (with the possible exception of vitamin A, calcium, magnesium and biotin) is included in an amount equal to or greater than the minimum daily requirement in man. Further, it is preferred that the vitamins and minerals included in the inventive formulation are similar to those included in the multi-vitamin and mineral preparations Centrum0 or One-A-Day0 (as shown in Table 3).
WO 91/11117 2~ 7 PCI`/US91/00719 . .
,, , . ., !. ~, . CENTRUM~ ONE-A-DAY
Vitamin Amount %USRDA Vitamin Amount ~USRDA
Vitamin A 5000 I.U. 100% Vitamin A 5000 I.U. 100%
(as Acetate . ~a~ Beta & Beta Carotene) carotens) Vitamin A 1500 I.U. 3C%
(a~ Acetate) Vitamin E 30 I.U. 100% Vltamin E 30 I.U. 10 (a~ DL-Alpha Tocopheryl Acetate) Vitamin C 60mg 100% Vitamin C 60mg 10~
(a~ Ascorbic Acid) ~:
Folic Acid 400 mcg 100~ Thiamine(Bl) 1.5mg 10~
Vitamin 81 1.5mg100% Riboflavin(B2) L~g 100%
(as Thiamine Mononitrate) -Vitamin B2 1.7mg100% Niacin 20mg 100%
(as Riboflavin) Niacinamide 20mg looe Vitamin D 400 I.U. 100% :.:
vitamin B6 2mg 100% Vitamin B6 2mg 100%
(ac Pyridoxine Hydrochloride) Vitamin B12 6mcg 100% Folic Acid 0.4mg 10 ~as Cyanocobalamin) Vitamin D 400 I.~. 100% vitamin Bl2 6mcg 10 Biotin 30mcg100% Biotin 30mcg 10%
Pantothenic Acid 10mg 100% Pantothenic 10mg 100%
Acid Calcium 162mg 16% Iron 18mg 10D%
(a~ Dibasic (elemental) Calcium Phosphate) Mineral Amount%USRDA Mineral Amount %USRDA
Pho~phorus 125mg 13% Calcium 130mg 13%
(as Dibasic Calcium Pho~phate) Iodine 150mcg100% Phocphorun 100mg 10%
~an Potacsium Iodine) Iron 18mg 100% Iodine 150mcg 10 (a~ Ferrou~ Fumarate) W091/11117 PCI`/US91/W7~
2~ ,7 Magne~ium lOOmg 25% Magneuium lOOmg 25%
(a~ Magne~ium Oxide) . .
Copper 2mg 100% Copper 2mg 10(as Cupric Oxide) Zinc 15mg 100% Zinc 15mg 10~ , (a~ Zinc OxLde) Mangane~e 2.5mg * Chromium lOmcg Pota~ium 40mg ~ Selenium lOmcg * `~
(as Potas~ium Chloride) Chloride 36.3mg * Molybdenum. lOmcg *
(as Potas~ium Chloride) Chromium 25mcg ~ Mangane~e 2.5mg *
(as Chromium Chloride) Molybdenum 25mcg ~ Pota~sium 37.5mg *
(a~ Sodium Molybdate) Selenium 25mcg ~ Chloride 34mg *
(a~ Sodium Selenate) Vitamin ~1 25mcg *
(a~ Phytonadione) Nickel Smcg *
(a~ Nic~el Sulfate) wo 91/11117 2~ PCT/US91/00719 f-33 ~ i. D ~ ' Mineral Amount ~USRDA Mineral Amount %USRDA
Tin lOmcg ~ .
(aQ Stannous Chloride) Silicon lOmcg *
(as Sodium Meta~ilicate) Vanadium lOmcg ~as Sodium Metavanadate) *No U.S. RDA establi~hed It is known that certain amino acids are essential for proper cellular function. However, it has been suggested by researchers that select amino acids provide some protection against cancer, and may, in fact, act synergistically with the preferred antioxidants of the present invention to protect against cancer. Thus, it is one important aspect of the present invention to provide a daily dietary multi-vitamin and mineral supplement including antioxidants and select amino acids. According to one embodiment of the invention, the preferred antioxidants are selected from the group consisting of BHT, BHA, propyl gallate, and sodium benzoate, and the preferred amino acids or analogs are selected from the group consisting of glutathione, cysteine, methionine, glutamine, and taurine.
Accordingly, one preferred embodiment of the present invention provides a daily dietary multi-vitamin and mineral supplement including, in combination:
(a) from about lO to about 300 mg of BHT;
tb) from about lO to about 300 mg of BHA;
(c) from about l to about 300 mg of sodium benzoate;
and (d) from about lO to about 300 mg of propyl gallate.
(e) from about l to about 20 mg of glutathione;
(f) from about 5 to about lO0 mg of cysteine;
(g) from about l to about 20 mg of methionine;
, WO91/111~7 ' ' PCT/US91/00719 2~7 '' ~7 ~ . ~
- 34 - '~
~ (h) from about l to about 20 mg of glutamine;
,:' (i) from about 2 to about 200 mg of bioflavonoids;
(j) from about l0 to 500 mg of potassium sorbate/sorbic acid; .:
(k) from about l to about 20 mg of taurine;
~l) from about 5,to 500 units of catalase as a food concentrate; and :
(l) from about 20 to about 500 units of SOD, as a food concentrate.
More preferably, however, the supplement includes:
(a) about 50 mg of BHT; ..
(b) about 50 mg of BHA; .
(c) about 4 mg of sodium benzoate; and (d) about 50 mg of propyl gallate.
(e) about l0 mg of reduced L-glutathione;
(f) about 50 mg of L-cysteine HCl; ,' (g) about l0 mg of DL-methionine;
(h) about l0 mg of DL-glutamine; and ' (i) about l00 mg of biofl,avonoids; - .. ~
(j) about 200 mg of potassium sorbate/sorbic acid; ~;
(k) about l0 mg of taurine; .,~
(l) about 150 units of catalase as a foo.d concentrate; and ~' (m) about 150 units of SOD as a food concentrate. .~
2~ :
In addition to the antioxidants and amino acids described above, several other ingredients may be included in the formulations of the invention, including:
(a) omega-3 fish oil;
(b) para-aminobenzoic acid (PABA); and .
(c) inositol.
'. -It has been demonstrated that several vitamins and minerals act synerg~stically in combination with several of the preferred antioxidants and amino acids of the ~,;
invention; therefore, it is an important aspect of the ~:.
present invention to provide formulation including these . '~
-.' ' ` , .: : - ;- . .
wo 91/11117 2~ ~ 5~ PCT/US91/00719 ... . . .
vitamins and minerals in appropriate amounts. Accordingly, a preferred embodiment of the present invention provides a daily dietary multi-vitamin and mineral tablet including, in combination:
(a) from about 10 to about 300 mg of BHT;
(b) from about lO to about 300 mg of BHA;
(c) from about 1 to about 300 mg of sodium benzoate;
(d) from about 10 to about 300 mg of propyl gallate.
(e) from about 1 to about 20 mg of glutathione;
( f ) from about 5 to about lO0 mg of cysteine;
(g) from about 1 to about 20 mg of methionine;
(h) from about 1 to about 20 mg of glutamine;
(i) from about 1 to about 20 mg of taurine;
(j) from about 1000 to about 3000 i.u. of vitamin A;
lS (k) from about 2500 to about 7500 i.u. of beta carotene;
(l) from about lO to about 100 i.u. of vitamin E;
(m) from about 10 to about 1000 mg Ca ascorbate; and (n) from about 10 to about 500 mg potassium sorbate or sorbic acid.
More preferably, however, the supplement includes:
(a) about 50 mg of BHT;
(b) about 50 mg of BHA;
(c) about 4 mg of sodium benzoate; and (d) about 50 mg of propyl gallate.
(e) about 10 mg of reduced L-glutathione;
(f) about 50 mg of L-cysteine HCl;
(g) about 10 mg of DL-methionine;
(h) about 10 mg of DL-glutamine;
(i) about 10 mg of taurine;
(j) about 2000 i.u. of vitamin A acetate;
(k) about 5000 i.u. of beta carotene;
(l) about 100 i.u. of vitamin E, DL alpha tocopheryl acetate;
(m) about 250 mg calcium ascorbate; and (n) about 200 mg of potassium sorbate or sorbic acid.
- .
:' ' .: ':,. ' :''' ' - . , ~ . , :
: ~' " , : . ' `, ~ .`;' ', ' ', ' ,-:' . ' .. : ''. ' .', ' ' -.. . . . . . .
WO91/11117 ~ PCI~U591/U071 ~ ~
2~ 36 -The inventive supplement includes many vitamins and minerals which are commonly used in commercially available , -multi-vitamin and mineral preparations. Preferably, the supplement of the present invention includes the following vitamins and minerals in an amount equal to or greater than the minimum daily requirement in man: ' (a) vitamin C;
(b) folic acid;
(c) vitamin Bl; :
(d) vitamin B2;
(e) niacinamide;
(f) vitamin B6;
(g) vitamin B~2;
(h) vitamin D3;
(i) biotin; -;~
(j) pantothenic acid;
(k) vitamin K~
(1) calcium;
. (m) iodine;
(n) potassium;
(o) iron;
(p) magnesium;
(q) copper;
(r) zinc;
(s) manganese; ~`
(t) chromium;
(u) molybdenum;
(v) selenium;
(w) vanadium;
(x) silicon; and (y) boron.
~ The formulations of the present invention contain a . number of vitamins and minerals similar to other multivi$a-min formulations, e.g, Centrum~. However, the formulation ~ --- ... .. . " ., ., . . , ~ . . , : -:: - . . . .
WO91/11117 2~ PCT/US91/00719 ,~ ~
of the present invention provides those vitamins and miner-als in amounts which better reflect the scientific data concerning these agents. For example, the amount of vitamin A included in the present invention is less than in other available formulations because it can be toxic to older people. Further, the amount of beta-carotene included is greater because it is nontoxic and provides improved benefits. For the above reasons the vitamins and minerals included in the present invention offer a broader base of vitamins a~d minerals than presently available in the industry; thus, providing the public with a comprehensive multivitamin useful in the prevention of heart disease and cancer.
According to one preferred embodiment, the vitamins and minerals included in the inventive formulation includes:
VITAMINS
(a) Vitamin A acetate from about lO00 to about 3000iu; (b) Beta carotene from about 3000 to about 6000iu;
(c) Vitamin E, DL alpha tocopheryl acetate from about 20 to about 40 iu;
(d) Calcium ascorbate from about 200 to about 400mg;
(e) Folic acid from about 200 to about 600mcg;
(f) Vitamin Bl from about l.0 to about 2mg;
(g) Vitamin B2 from about l.5 to about 2mg (h) Niacinamide from about lO to about 30mg;
(i) Vitamin B6 from about l to about 3mg;
(j) Vitamin B~2 from about 4 to about 8mcg;
(k) Vitamin D3 from about 400 to about 800iu;
(l) Biotin from about 20 to about 40mcg;
(m) Calcium pantothenate from about 5 to about 15mg;
and (n) Vitamin Kl from about 15 to about 35mcg.
- ~ . : . . . ,- - -. . . .
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W09ltllll7 PCr/US91/00719 2~ i~;~ 7 -- 38 MINERALS
(a) dicalcium phosphate from about 50 to about 150 mg;
(b) potassium iodide sufficient to supply from about 100 to about 150 mcg of iodine;
(c) potassium chloride sufficient to supply from ~ :
about 20 to about 60mg of potassium; .
(d) ferrous fumarate sufficient to supply from about 16 to about 30mg of iron; ~.
(e) magnesium oxide sufficient to supply from 75 to about 12Omg of magnesium;
(f) copper oxide sufficient to supply from about 1 to ~:
about 3mg of copper;
(h) zinc oxide sufficient to supply from about 10 to about 20mg of zinc;
(i) manganese gluconate sufficient to supply from about 1 to about 3mg of manganese;
(j) chromium (+3)chloride sufficient to supply from about 15 to about 35mcg of chromium;
(k~ sodium molybdate sufficient to supply from about 15 to about 35 mcg of molybdenum;
(l) sodium selenate sufficient to supply from about 15 to about 35mcg of selenium;
(m) sodium metavanadate sufficient to supply from about to about 15mcg of vanadium;
(n) sodium metasilicate sufficient to supply from about 5 to about 15mcg of silicon; and -~
(o) boron from about 1 to about 3mg. ~
~ ':
It should be noted, however, that other vitamins and minerals not listed above may be added to the formulations of the present invention without departing from the spirit of the present invention. ~ :
. .
However, according to the most preferred embodiment, the vitamins and minerals of the present invention include~
2~ 5~7 . ., ~,~, VITAMINS
(a) about 2000 i.u. of vitamin A acetate;
(b) about 5000 i.u. of beta carotene; ~:-(c) about 30 i.u. of vitamin E, DL alpha tocopheryl acetate;
(d) about 250mg of calcium ascorbate;
(e) about 400mcg of folic acid;
(f) about 1.5mg of vitamin B~
(g) about 1.75mg of vitamin B2;
(h) about 20mg of niacinamide; :.
(i) about 2mg of vitamin B6;
(j) about 6mcg of vitamin B12;
(k) about 6bo i.u. of vitamin D3; -::
(l) about 30mg of biotin; '~ --(m) about lOmg of calcium pantothenate; and ;
(n) about 25mcg of vitamin Kl. ~:
MINERALS :
_ _ .
(a) about lOOmg of dicalcium phosphate; ::
(b) potassium iodide sufficient to supply about 125mg :
iodine;
(c) potassium chloride sufficient to supply about :~ .
40mg of potassium;
(d) ferrous fumarate sufficient to supply about 20mg -.
of iron;
(e) magnesium oxide sufficient to supply about lOOmg of magnesium;
(f) copper oxide sufficient to supply about 2mg of copper; ~:
(h) zinc oxide sufficient to supply about 15mg of zinc;
(i) manganese gluconate sufficient to supply about 2mg of manganese;
(j) chromium (+3)chloride sufficient to supply about :
25mcg of chromium; :~
z~7 ~ 5~7 40 (k) sodium molybdate sufficient to suppIy about 25mcg of molybdenum;
(l) sodium selenate sufficient to supply about 25mcg of selenium;
(m) sodium metavanadate sufficient to supply about lOmcg of vanadium;
(n) sodium metasilicate sufficient to supply about lOmcg of silicon; and (o) about 2mg of boron.
The protective agents included in the inventive formulations are either already approved by the FDA or generally regarded as safe (GRAS) by the FDA or are generally thought to be safe by scientific experts. These agents include antioxidants, amino acids, and enzymes, which have been shown to be effective in preventing the induction of cancer and cardiovascular disorders as well as extending the life span of experimental animals. Further, a number of the ingredients have been shown to act synergistically with other agents in the formulation. This combined effect should increase their protective effects.
For example, selenium and vitamin E work synergistically against the induction of breast cancer. Further, in a number of studies, BHA when given with vitamin A, beta-carotene and vitamin E was shown to provide a protection against cancer. Accordingly, the present invention is directed to a multi-vitamin dietary supplement formulation, and methods for producing and administering the same to an individual in need thereof. It is believed that the present invention provides a formulation which is cardio-and cancer-protective.
A further aspect of the present invention is directed to a method for producing the formulations of the present invention. Preferably, the formulation is tableted, and most preferably, the formulation is tableted as a sustained release tablet. The sustained release tablets of the p~. ,~. , . . . . . , . . ~.
-. :- -. . ~ . .
. : . : . :.: . . . . :
WO91/11117 PCT/~S91/00719 - 41 - : ~
present invention are intended to provide for the extended action of the ingredients from a single dose. Thus, the sustained released tablet is a convenient dosage form by virtue of eliminating the necessity for dosage several times during the day. Moreover, therapeutic benefits may also be obtained by the sustained release of the active ingredients of the inventive formulation. It is believed desireable that the sustained release dosage form of the present invention will provide a slow and constant supply of antioxidants, amino acids, and other beneficial dietary supplements which will provide protection against cancer and cardiovascular disease throughout the day.
In order to stabilize the preparations of the present lS invention, it has been determined that several of the more reactive constituents are preferably microencapsulated.
The microencapsulation of select constituents prevents those constituents from reacting with other ingredients if left unchecked, which would shorten the shelf life of a commercial product embodying the inventive formulation.
According to one embodiment, the preferred sulfur-containing amino acids and the polyunsaturated acids are microencapsulated. More specifically, glutathione, cysteine, and omega-3 fish oil are preferably microencapsulated when included in the invented formulation.
According to one preferred embodiment, hydroxypropyl methylcellulose is used as a pharmaceutical adjunct which provides a sustained release of the active constituents of the tablet. According to this preferred embodiment, based upon the physical parameters involved in formation of a tablet which is determined by the nature of the ingredients (compressibility, adhesion of particles, etc.), up to 20%
of the dry weight could be required for hydroxypropyl methylcellulose to ensure proper time release tablet.
Thus, according to one embodiment, a total formulation . ~, . : ~ . , . - :,. .: .
W~91/11117 PCT/US91/00719 z~ ~5,, ~ - 42 -weight range, including time released material, would have a weight range of from about 4090 mg to about 3526 mg.
Because of the bulk of the formulation, the formulation is preferably produced and administered as 1-3 tablets daily.
, The following examples are presented to describe specific preferred embodiments and utilities of the present invention and are not meant to limit the present invention unless otherwise stated in the claims appended hereto.
EXAMPLES
In vitro disintearation characteristics A comparison was made between the relative disintegrations of Centrum tablets and the sustained release tablets of the present invention.
As a measurement of disintegration, the release of four different vitamins, potassium, vitamin C, niacinamide, and pyridoxine was measured. The results, summarized in Figs. 1-6, show that the sustained release tablet of the present invention provides for uniform disintegration over at least seven hours.
As a general procedure, gastric and intestinal juices were prepared according to the United States Pharmacopeia XVIII. The dissolution tests were conducted using the apparatus specified for such procedures in the National Formulary XIII. The apparatus generally consisted of a horizontal rotating shaft to which was attached clamps for holding round cylinders approximately 150mm long and having a diameter of approximately 30 mm wherein the tablets were contained. The apparatus then submerges the tablets in the appropriate dissolution fluid. The temperature of the dissolutions fluid was maintained at 37+ 2 C throughout the study. Eight tablets were used to generate the dissolution .: : . : ~ . ~ : .: . -: : .
WO91~11117 PCT/US91/00719 1 2~ ~ ~ 43 _ ,~
data. Six Centrum (UDC0005-4239-13 Lederle Laboratories Division American Cyanamid Company) and two sustained release tablets of the present i~vention, which were prepared as follows.
The following shows the content and instructions for preparing a most preferred formulation (300,000 tablets 3 tablet/dose) of the present invention.
Weight Range Per Do~e ~dose = 1 dav su~lv) G _ vitamins 5.4 mgVitamin A acetate 2000 iu from 500,000 iu/gm beadlet~ with 35% overage 540 40.5 mgBeta carotene 5000 iu = 30 mg with 35% overage from 10% beadlets 405 231 mg Vitamin E DL alpha tocopheryl acetate 100 iu from 50% 2.1 mg finished material with 10% overage 23,100 300 mg Calcium ascorbate = 250 mg with 20% overage 30,000 mg Follc acid as 10% trit = 400 mcg/do~e with 25%
overage 500 1.73mg Vitamin Bl dose = 1.5 mg with 15~ overage173 1.87mg Vitamin B2 dose = 1.7 mg with 10% overage187 3022 mg Niacinamide dose = 20 mg with 10% overage2,200 2.67mg Vitamin B6 dose = 2 mg with 10% overage 267 0.75mg Vita~in B12 dose = 6 mcg from 1% trit on re~in with 25% overage 75 8.1 mg Vitamin D3 dose = 600 iu from 100,000 iu/gm with 35% overage 810 403.3 mg BiotLn do~e = 30 mcg from 1% trit with 10% overage 330 14 mg Calcium pantothenate dose = 10 mg with 30~ overage 1,400
Vitamins and minerals may be broadly defined as -substances that are essential for the maintenance of normal metabolic function but are not synthesized in the body.
These substances must be furnished from an exogenous source. A healthy individual ingesting a well-balanced diet receives adequate amounts of vitamins and minerals ;-from food. Vitamins obtained in this manner are not generally regarded as drugs.
However, there are many situations in which the concentration of one or more vitamins or minerals in the body tissues may be suboptimal. When such circumstances arise or can be anticipated, it is the common practice to administer vitamins or minerals in a chemically pure form.
When employed in this manner, vitamins and minerals may be regarded as drugs and a knowledge of their pharmacological properties is desirable. For example, large doses of various vitamins are frequently employed for the treatment of disorders that are not etiologically related to vitamin deficiency. The implication is that such large doses may exert pharmacodynamic actions that are useful in therapy.
' '' ' .
It should be noted, however, that excessive administration of certain vitamins, notably vitamin A, can cause untoward toxic effects.
In today's fast paced society many physicians and dieticians believe that a daily dietary vitamin and mineral : - ., .: , . ~...................... . . .
: :. . .... . . :. .............. .. - : ,- .: , -.. . . . , . . . ~. . ~ .
. . . .. . . .
2~7~ J~ - 2 -supplement acts prophylactically to prevent pathologies associated ~ith vitamin and mineral deficiencies. These supplements typically include several vitamins and minerals, and are referred to as multi-vitamin formulations. Examples of these preparations include One-A-Day~ and Centrum~ multi-vitamins. Researchers have suggested that multi-vitamins which include large quantities of vitamins and minerals are effective both for prophylactic purposes and for the treatment of an enormous variety of illnesses. Many millions of individuals living in the United States regularly ingest multi-vitamin preparations.
Some of these multi-vitamin preparations contain amounts of vitamins and minerals that are in excess of the RDA daily requirements. In the case of the water-soluble vitamins, there is little harm done to the body because of the low toxicity of this class of compounds. The low toxicity of the water-soluble vitamins is attributable to the fact that excess quantities of these substances are rapidly excreted in the urine. In the case of the lipid-soluble vitamins, the compounds accumulate in the body fat and can cause untoward toxic effects.
It is extremely important to distinguish between supplemental and therapeutic vitamin preparations. The latter contains much larger quantities of the individual vitamins and minerals than do the supplemental preparations. The present invention is directed to supplemental preparations.
The use of dietary multi-vitamin supplements should be considered by the physician in a wide variety of situations. Such situations may result from (l) inadequate vitamin intake, (2) mal-absorption syndromes, and (3) increased tissue requirements.
.. . ... . ,.,. , - . , - ,-, , ,. . - .
~ ~ .
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Vitamin deficiency due to an inadequate intake arises in a variety of circumstances. There are still large parts of the world and even considerable areas in the United States where, owing to poverty, the population eats a diet inadequate in terms of vitamin content. Moreover, there are areas where the prevalence in the diet of one particular type of food results in a relatively high incidence of vitamin deficiencies. Eccentric diets resulting from psychiatric disturbance, individual idiosyncrasies, religious beliefs, or food fads are other major causes of vitamin deficiency. A decrease in food consumption because of excess use of alcoholic beverages, poor appetite, dieting to combat obesity, or restricted diets prescribed by physicians for the management of specific diseases represents a further group of situations in which vitamin deficiency can arise.
A disturbance in absorption of vitamins is also seen in a variety of conditions. Examples are diseases of the liver and biliary tract, prolonged diarrhea from any cause, hyperthyroidism, pernicious anemia, and a variety of other disorders of the digestive system. Moreover, since a substantial proportion of certain vitamins is provided by the bacteria of the gastrointestinal tract, treatment with antimicrobials that alter the intestinal bacterial flora may lead inevitably to a decreased vitamin absorption.
Increased tissue requirements for vitamins also occur under a variety of conditions so that a nutritional defi-ciency may develop on a diet that had previously been adeguate. Such situations can occur in both health and disease. In healthy individuals, for example, there is a greater requirement for various nutrients, including vita-mins, during growth, during periods of hard physical work, exercise, during pregnancy, lactation, and menstruation.
Diseases associated with an increased metabolism, such as hyperthyroidism, and conditions accompanied by fever or ..
~' .
2~ 7 - 4 tissue wasting also increase the body~s requirements for vitamins. There is also good evidence that vitamin requirements increase during stress and after injury.
Multiple-vitamin therapy, using supplemental dietary multi-vitamins, is desirable in a variety of situations.
Since deficiency of a single vitamin is rarely encountered clinically, it is customary practice in cases of suspected vitamin deficiency, as well as in prophylactic treatment, to recommend that multiple-vitamin therapy be administered.
Typical of the multi-vitamins available are One-A-Day and Centrum multi-vitamins. (Table 1). Multi-vitamins such as these provide a great number of the essential vitamins and minerals needed by healthy individuals. Further, these preparations include electrolytes, and trace elements.
Recently, it has been determined that antioxidants, and free radical scavenging agents are protective against the development of certain cancers. Although, multi-vitamin preparations currently available include many needed vita-mins and minerals, they do not include the antioxidants and/or free radical scavengers which have been shown to enhance the immune system and to prevent certain cancers, cardiovascular disorders, inflammatory diseases and to slow ageing. Further, currently available multi-vitamin preparations do not include cardio-protective inositol or Omega-3 fish oils. Still further, several enzymes, amino acids, and dietary supplements which are known to be neces-sary and beneficial in supplementing an individual's diet are not included in presently available multi-vitamins.
Accordingly, a new multi-vitamin dietary supplement is needed which incorporates many of these beneficial ingredi-ents into a stable pharmaceutical preparation.
The present invention concerns development of a multi-vitamin dietary supplement formulation which includes several dietary supplements which are cardio- and cancer-protective as well as immunostimulatory. By including ,' ' . '.i................................ . ............. ...
' ~: '. ' ' . . ' : , ' ' ' ' ' ' '. :
wo g~ 7 .2~?~`1i ~ ~7 Pcr/usgl/oo7lg f `~
these cardio- and cancer-protective immunostimulatory compounds into a multi-vitamin formulation, the present invention advantageously provides the general population the benefits of recent scientific research which has S discovered that several agents are, for example, cardio-and cancer-protective. Accordingly, it is believed that the inventive methods and formulations will provide the general population with an improved multi-vitamin formulation capable of reducing the incidence of diseases such as heart disease and cancer while enhancing longevity and the immune system.
The present invention is directed to a formulation including vitamins, minerals and other beneficial supplements. More specifically, the invention is directed to a formulation and methods of manufacturing an*
administering a formulation containing vitamins and minerals in association with antioxidants, fish oils, food concentrate containing naturally occurring anti-oxidizing enzymes such as catalase and superoxide dismutase, for example, and amino acids. The formulations of the present invention exploit synergistic relationships which have not previously been reported.
One aspect of the present invention is directed to a multi-vitamin and mineral supplement which includes at least one antioxidant selected from the group consisting of BHT, BHA, propyl gallate, and sodium benzoate.
Several of the antioxidants, vitamins and minerals contained in the formulation have been shown to inhibit the induction of cancer at several stages in the multistage process. For example, B-carotene, glutathione, cysteine, 8HA, BHT, Vitamins A, C and E, as well as selenium, inhibit the tumor initiation, promotion and progression stages of cancer. The synergistic effects of BHA and Vitamin E, for example, are related to the observations that BHA inhibits :. , .~ . ............. . , .- ,: ~ , .
:., -, ~
W091/11117 PCT/US91tO0719 ~ ~?
2~7 ~ ;7 - 6 -tumor promoter-induced polyamine synthesis, and Vitamin E
inhibits promoter-induced hyperplasia, thus leading to a synergistic effect. Furthermore, Vitamins A, C and E, selenium, BHA, BHT, and propyl gallate have been shown to inhibit tumor initiation by counteracting the covalent binding of carcinogen to DNA and the mutagenic effect of carcinogens.
A further aspect of the present invention is directed to a multi-vitamin and mineral supplement including antioxidants in combination with certain preferred amino acids selected from the group consisting of glutathione, cysteine, methionine, glutamine, and taurine. According to a preferred embodiment, the inventive formulation further includes at least one of the following beneficial ingredients: omega-3 fish oil, para-aminobenzoic acid,;
superoxide dismutase, catalase (these two enzymes being preferably in food concentrates), bioflavonoids, and inositol.
-Preferably, the supplement of the present invention includes (but is not limited to) the following vitamins and minerals in an amount equal to or greater than the minimum daily requirement in man: vitamin C, folic acid, vitamin Bl, vitamin B2, niacinamide, vitamin B6, vitamin Bl2, vitamin D3, biotin, pantothenic acid, vitamin Kl, calcium, iodine, potassium, iron, magnesium, copper, zinc, manganese, chromium, molybdenum, selenium, vanadium, silicon, and boron.
An important aspect of the present invention is directed to a method for preventing cancer and cardiovascular disorders as well as increasing longevity and augmenting the immune system in a human subject. The method including the step of administering daily an oral sustained release tablet including the dietary multi-.
WO91/11117 2~ ~5~7 PCT/US91/00719 . ~,. ' ' ' ~ --' t - 7 - ~-vitamin and mineral supplement including antioxidants and other beneficial substances of the present invention.
! ~ ' A still further aspect of the present invention is directed to the production of a sustained-release tableted dietary supplement which is intended to be administered one to three times daily.
FIG. l graphically represents, as a function of %
potassium released versus time, the dissolution of Centrum tablets in gastric juice. ;
FIG. 2 graphically represents, as a function of %
potassium released versus time, the dissolution of the sustained release tablets of the present invention in intestinal juice.
FIG. 3 graphically represents, as a function of %
ascorbic acid released versus time, the dissolution of the sustained release tablets of the present invention in intestinal juice.
: .
FIG. 4 graphically represents, as a function of %
niacinamide released versus time, the dissolution of the sustained release tablets of the present invention in intestinal juice.
~, FIG. 5 graphically represents, as a function of pyridoxine % released versus time, the dissolution of the sustained release tablets of the present invention in intestinal juice.
The present invention concerns a formulation of vita-mins, minerals and other beneficial supplements. It is believed that the formulations of the present invention will not only extend longevity but also protect against certain cancers, immunological disorders and cardiovascular , WO91/11117 ~ PCT/US91/00719 2~ 8 disorders in humans. Generally, the invention is directed to a formulation and methods of manufacturing and administering a formulation containing vitamins and minerals in association with antioxidants, fish oils, anti-oxidizing enzymes preferably contained in food concentrates, and amino acids. It is believed that the formulations of the present invention will be beneficial in treating or preventing several pathologies, including various vitamin deficiencies, certain cancers, immunological disorders, and cardiovascular disease.
The formulations of the present invention exploit some synergistic relationships which have not previously been reported. The formulations of the present invention are particularly well adapted as a daily dietary supplement.
The present invention further involves a method for administering the formulations of the present invention to a person in need thereof. The preparation of the present formulations is also a component of the present invention.
Table l shows the anti-cancer effects of various components of the present formulation, individually and in synergistic combination.
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Table 1 Effects of antioxidant~ on 8kin Tumor Promotion-Antioxidant Tumor Response (mg) (% Inhibition) Control (DMBA + TPA) o BHA (0.5) 35 BHT (0.5) 32 Propyl gallate (0.5) 40 Vitamin E (0.1) 25 Vitamin C (0.5) 30 B-carotene (0.5) 20 Selenium (0.004) 23 BHA (0.5) + BHT (0.5) 92 BHA (0.5) + Vit E (0.1) 86 BHA (0.5) + Vit C (0.5) 98 Vit E (0.1) + Selenium (0.004) 94 Vit E (0.1) + B-carotene (0.5) 94 BHA (0.5) + B-carotene (0.5) 87 -BHA(O.l)+BHT(O.l)+Vit E(O.l)+B-carotene(0.1) 97 ^30 female mice (SENCAR) per group were used. The mice were initiated with 10 nmoles of 7,12-dimethylbenzanthracene and promoted with 1 ug of TPA 2x/~k. The antioxidants were applied simultaneously with TPA for the duration of experiment (30 weeks).
Table 2 illustrates the effects of certain antioxidant components of the present formulation on all the known spontaneous tumor formations and longevity in mice.
- :~
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2~ o -~able 2 Effects of Antioxidants on Aging and ~pontaneou~ Tumor Formation in ~ice- -Antioxidantsb Spontaneous Tumor Formation Increase in (% of Control) Lifespan (%~
Normal Diet lOO
Propyl gallate 62 127 ~100 mice (SENCAR) (50 males and 50 females) were used for each group. The groups receiving the antioxidants had them introduced in the normal laboratory chow (Wayne Research Animal Diet) at 0.5%.
Core ingredients in the most preferred formulation of the present invention are antioxidants and/or free radical scavenging agents of different types which protect against many kinds of free radicals and unstable molecules. In some cases, they work synergistically with other antioxidants, vitamins, and minerals. The following are the Core ingredients:
bioflavonoids L-glutathione (reduced) L-Cysteine Potassium sorbate/sorbic acid BHA
BHT
Propyl gallate Sodium benzoate Taurine D L-Methionine L-glutamine SOD and Catalase (preferably contained in food concentrate) ::.`: - - -- : :. 7 : :~ - ,: . . ..
. :, .
2~?7~
-- 11 -- .
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The significance and content of the Core ingredients may be described as follows: -- ' ~':
Bioflavonoids are ~iologically active compounds that have been shown to act as antioxidants, protecting vitamin C and other components from oxidation. certain bioflavonoids have been shown to have a protective effect against some cancers. The dosage of the bioflavonoid included is from about 2 to 200 mg, more preferably, from about 25 to about 150 mg, and most preferably, about 50 mg.
Preferable sources of bioflavonoid include citrus ;
bioflavonoid, vitamin P, vitamin P complex, rutin, orange peel bioflavonoid, grapefruit peel bioflavonoid, lemon bioflavonoid, lime bioflavonoid, flavonoids, kaempferol, narigenin, apigenin, naringin, naringenis, myricetin, delphinidin, quercetin, phloretin, cyanic, catechin, morin, phloridzin, phloretin, 3-hydroxyflavones, 3-deoxyflavonols, isorhamnetin, luteolin, tricin, chrysoeriol, hesperitin, eriodictyon, techtrochrysin, silybin, taxifolin, pinocembrim, galangin, robinin, diosmetin, kaempferide, fisetin, rhamnetin, and 3-0-methyl catechin. The most preferable source is, however, citrus bioflavonoid.
It is believed that glutathione may protect normal cells against radiation, free radicals and other toxic materials, and certain cancers. Functionally, glutathione is the proton donor used by glutathione peroxidase to remove free -radicals. Forms of glutathione useful in the practice of the present invention include: L-glutathione, S-ethylglutathione, S-butylglutathione, S-decylglutathione, S-heptylglutathione, S-methylglutathione, S-propylglutathione, S-pentylglutathione, S-octylglutathione and S-nonylglutathione. However, most preferably, glutathione is included in the formulations of the present invention as reduced L-glutathione. The dosage of glutathione included to the inventive formulation is .. ", ., ~, ~, ., . , . . . , - , . .
- ~ .
WO91/11117 PCT/US91/0071~ ~
':
2~7 A ~ l2 -preferably from about l to about 29 mg, and most - preferably, about lO mg.
L~Cysteine is an amino acid which has antioxidant propertieC and plays an important role in glutathione peroxidase activity. Cysteine also appears to have certain anticancer activity. Preferably, cysteine is included in the present invention as L-cysteine HCl, L-cysteine, L-acetyl cysteine, L-cysteine ethylester monohydrochloride, DL-cysteine, DL-cysteine HCl, L-cysteine methylester.
However, it is most preferred, that cysteine is included as L-cysteine HCl, in a dosage of from about 5 to about lOo mg, and more preferably, about 50 mg.
::
Potassium sorbate and/or Sorbic acid are useful as a mold and yeast prohibitor. Sorbic acid has been shown to increase the effectiveness of antioxidant mixtures by acting synergistically with them. The sorbic acid dosage is preferably from about lO to 500 mg as potassium sorbate, sorbic acid, or sodium sorbate. Most preferably, however, the dosage of sorbic acid is about 200 mg as potassium sorbate.
In one important aspect of the present invention, the formulation includes at least one antioxidant. The antioxidant is preferably selected from the group consisting of butylated hydroxyanisole, butylated hydroxytoluene, propyl gallate, and sodium benzoate. The inventive formulation may include one, or, more preferably, several of the preferred antioxidants in combination.
According to one embodiment, the inventive formulation includes butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), sodium benzoate, and propyl gallate.
Sodium benzoate, BHA, BHT and propyl gallate are all antioxidants used to -stabili~e cosmeticj pharmaceutical, and food products. It has been reported that these agents protect normal cells against radiation, free radicals, .. .'- . . ', : ,' ' ~ :': ' .,., ~' ' . , ' ' WO91/11117 ~ PCT/US91/00719 - 13 - ~ .
toxic chemicals and chemical carcinogens. It has also beën reported that these agents are protective against the induction of cancer by many cancer-causing agents in almost every tissue of the body. Further, the preferred antioxidants of the present invention have been reported to protect against cardiovascular disorders, enhance immune function and increase longevity. The preferred antioxidants of the present invention work synergistically with several vitamins, minerals, amino acids, enzymes, and other antioxidants or free radial scavengers included in the formulation of the present invention as will be described in detail below.
According to one embodiment, BHA is included in a daily dietary multi-vitamin and mineral formulation for humans administered on a 1-3 times daily basis. Preferably, from about l to amount 300 mg of BHA is included in combination with a number of vitamins and minerals. More preferably, however, the formulation includes from about lO to about 150 mq of BHA, and most preferably, about 50 mg of BHA.
BHA may be included in the inventive formulation as butylated hydroxyanisole, 3-tert-butyl-4-hydroxyanisole, or 2-tert-butyl-4-hydroxyanisole, but most preferably is butylated hydroxyanisole.
According to another preferred embodiment, BHT is included in a daily dietary multi-vitamin and mineral formulation. Preferably, from about l to amount 300 mg of BHT is included in combination with a number of vitamins and minerals. More preferably, however, the formulation includes from about lO to about 150 mg of BHT, and most preferably, about 50 mg of BHT.
According to further embodiment, propyl gallate is included in the daily dietary multi-vitamin and mineral formulation. Preferably, from about l to amount 300 mg of propyl gallate is included in combination with a number of WO91/11117 PCT/~S91/~0719 2~7 ~ P~
vitamins and minerals. More preferably, however, the formulation includes from about lO to about 150 mg of propyl gallate, and most preferably, about 50 mg of propyl gallate.
Sodium benzoate, an antioxidant used to stabilize food and pharmaceutical products, according to another embodiment, is included in a d~ily dietary multi-vitamin and mineral formulation. Preferably, from about l to amount 300 mg of sodium benzoate is included in combination with a number of vitamins and minerals. More preferably, however, the formulation includes from about l to about 150 mg of sodium benzoate, and most preferably, about 4 mg of sodium benzoate. As described above, one embodiment of the inventive formulation includes sodium benzoate. However, it has been determined that potassium benzoate, benzoic acid, calcium benzoate, cuprous benzoate, cupric benzoate, manganese benzoate, nickel benzoate, magnesium benzoate are all also useful in the practice of the present invention.
2C Taurine is an amino acid used by the liver for conjugation with bile acids. It has also been suggested that taurine strengthens and stabilizes cellular membranes.
High concentrations of taurine are found in the brain.
Taurine, it is believed, acts in concert with the preferred antioxidants of the present invention to provide increased protection against cancer and certain cardiovascular diseases. Preferably, taurine is included in the formulations of the present invention in a dosage of from about l to about 20 mg, and most preferably, about lO mg.
Methionine is an essential amino acid which has antioxi-dant properties. Methionine is the principal source of methyl groups which are, in turn, transferred to many diverse acceptors in important physiological reactions, such as, methyl transferases. Methionine is preferably include in the formulations of the present invention as DL-methionine, L-methionine, S-adenosylmethionine, N-acetyl-.. ~ - .
WO91/11117 2f~ 5~ 7 PCT/US91/00719 ~.
methionine, S-methyl-DL-methionine-sulfonium chloride.
However, more preferably, methionine is included as DL-methionine, in a dosage of from about l to about 20 mg, and most preferably, about l0 mg.
Glutamine is an amino acid which serves as an amino donor in many reactions. Glutamine is critical for the de novo synthesis of purine and pyrimidine nucleotides. These nucleotides are critical to normal cell function and replication. Preferably, glutamine is included in the formulations of the present invention as L-glutamine, DL-glutamine, or N-acetyl-L-glutamine. However, most preferably, glutamine is included as L-glutamine, in a dosage of from about l to about 20 mg, and most preferably, about l0 mg.
Superoxide dismutase (SOD) stabilizes the formulations of the present invention and is an antioxidant. SOD
prevents the formation of singles oxygen, hydroxyl radicals and other reactive oxygen species. It is believed that SOD
can protect against cancer, cardiovascular disorders and increase longevity. The dosage included of SOD (superoxide dismutase) is preferably from about 20 to about 500 units, more preferably, from about l00 to about 300, and most preferably about 150 units (i.u.) (McCord/Fridovich units).
Preferable sources of SOD for the formulation of the present invention include purified liver SOD, bovine SOD, intercellular SOD, bovi~e liver SOD, erthrocytic SOD, extracellular SOD, vegetable culture SOD, vegetable SOD, bovine lyophilized liver SOD, fractionated liver SOD, fractionated erythrocyte SOD, and bacterial SOD. The most preferable source of SOD is, however, vegetable SOD, particularly as a food concentrate.
.
Catalase also stabilizes the formulations of the present invention and compliments SOD. Catalase converts hydrogen peroxide into water and oxygen. It is believed that , 2~ J7 - l6 -catalase protects against diseases such as cancer and cardiovascular disorders as well as increasing longevity.
The dosage of catalase included is from about 5 mg to 500 units, more preferably, from about lOO to about 300 units, and most preferably, about 150 units (i.u.) (Baker Units).
Preferable sources of catalase include that purified from bovine liver, fractionated liver, bacteria, Aspergillus niger, and vegetables. The most preferable source is, however, vegetables, particularly as a food concentrate.
~ ~:
The core antioxidants can also interact synergistically with the following components, vitamins and minerals which are antioxidants additionally included in the preferred formulation (Core II):
Vitamin A
B-carotene (beta-carotene~
Vitamin E
Ca Ascorbate Copper Zinc Manganese Selenium omega-3 fish oil inositol PABA
Due to their importance both in the prevention of cancer and cardiovascular disorders, omega-3 fatty acid, PABA and inositol are also an important part of the Core II
formulation.
The Core II ingredients may be described as follows:
Vitamin A is a fat soluble vitamin essential in cell differentiation, vision, immunity, healthy skin, hair, and mucous membranes. This vitamin is also necessary for proper reproduction, bone growth and development of teeth.
Deficiencies have been associated with a higher incidence of certain cancers. Vitamin A appears to work synergistically with several other vitamins, as well as minerals and antioxidants, to lower cancer rates and to WO91/11117 2~ PCTtUSg1/00719 increase longevity. The dose of vitamin A preferably included is from about 1,000 to 3,000 i.u., and more preferably, about 2,000 i.u. Preferably, the vitamin A
source included in the formulation is vitamin A acetate, vitamin A palmitate, retinol, and retinal. The source of vitamin A may be water soluble, fat soluble, or emulsified.
Most preferably, however, the vitamin A source is emulsified vitamin A acetate.
Beta carotene or, provitamin A is a precursor to vitamin A. Beta carotene must be converted by the body into active retinol-type vitamin A to be utilized. Beta carotene is also a potent antioxidant and may prevent certain types of cancer. Beta carotene appears to work synergistically with several vitamins, minerals and antioxidants to lower cancer rates and to increase longevity. Although Vitamin A and other retinoids have been shown to inhibit the induction of skin cancer in mice, an unexpected result has been the lack of an inhibitory activity by B-carotene (beta carotene) in the mouse skin carcinoqenesis system. However, if B-carotene is given with low doses of vitamin E, BHA or BHT, it very effectively enhances their activity in a synergistic manner. The dosage of beta carotene included is preferably from about 2,500 to 7,500 provitamin A units as water soluble beta carotene, or emulsified beta carotene, and most preferably 5,000 provitamin A units as emulsified beta carotene.
Vitamin E is a fat soluble vitamin which functions as an antioxidant protecting lipid membranes against oxidation.
Deficiencies in vitamin E can increase the tendency of blood to clot. Vitamin E appears to work synergistically with several vitamins, minerals, e.g., selenium, and antioxidants to lower cancer rates and to increase longevity. The dosage of vitamin E included is preferably from about 10 to 100 units as DL-alpha tocopheryl acetate, DL-alpha tocopheryl succinate, water soluble DL-alpha .... ,, - ... - . ..
. . . ~ -. . . . . .
~ ... . . , . ~ -: .
: . , ~ : : . , . -: ,. ' .. ,, : : , . , :~ :
-2~ 18 tocopheryl acetate or succinate, emulsified DL-alpha tocopheryl acetate, D-alpha tocopheryl acetate, D-alpha tocopheryl succinate, mixed tocopherols, emulsified D-alpha tocopheryl acetate, emulsified mixed D-tocopherols, water soluble D-alpha tocopheryl acetate, water soluble mixed D-tocopherols, D-alpha tocopherol, emulsified D-alpha tocopherol, water soluble D-alpha tocopherol, or alpha tocopheryl nicotinate. Most preferably, however, the dosage of vitamin E is about lO0 units as vitamin E, DL-alpha tocopheryl acetate.
Vitamin C is a water soluble essential vitamin. It is critical in producing and maintaining collagen, promotes healing of wounds, aids tooth and bone formation, and is important in producing hormones that regulate basal metabolic rate and body temperature. Vitamin C also acts as an antioxidant and may counteract nitrosamines formed in the intestinal tract, and, therefore, helps reduce the rates of certain kinds of cancers. Vitamin C appears to work synergistically with several other vitamins, as well as minerals and antioxidants, to lower cancer rates and to increase longevity. The dosage of vitamin C included is preferably from about lO to l,000 mg as ascorbic acid, or salts of ascorbic acid including calcium ascorbate, magnesium ascorbate, sodium ascorbate, potassium ascorbate, esterified ascorbic acid, ascorbyl palmitate. Most preferably, however, the dosage of vitamin C is about 250 mg as calcium ascorbate. -~
Copper is a trace mineral essential for the formation of red blood cells and the utilization of iron. It also functions in electron transport, connective tissue metabolism and the development of the nervous system. ~ ;~
Deficiencies have been linked to nervous system disorders, bone disorders (spontaneous fractures) and anemia. Copper may protect against certain types of cancers. Copper dosage is 0.2 to 20 mg as copper oxide, cupric acetate, - "
-- 1 9 -- ~ ~ ~
cupric butyrate, cupric subcarbonate, cupric chloride, cupric citrate, cupric formate, cupric gluconate, cupric glycinate, cupric hydroxide, cupric oxide, cupric stearate, cupric sulfate, cupric subsulfate, copper gluconate, copper amino acid chelate, copper salicylate, copper proteinate, cupric tyrosinate, copper glycerophosphate, and copper picolinate.
zinc is a trace mineral essential to cell multiplication, tissue regeneration and wound healing, sexual maturity, and proper growth. zinc is required for many enzymatic functions throughout the body, and also helps regulate the immune system and insulin metabolism.
Preferably, the dosage of zinc included is from about dosage 2 to about 30 mg as zinc oxide, zinc acetate, zinc benzoate, zinc caprylate, zinc carbonate, zinc chloride, zinc citrate, zinc formate, zinc lactate, zinc selenate, zinc stearate, zinc sulfate, zinc picolinate, zinc gluconate, zinc sulfate heptahydrate, zinc sulfate monohydrate, zinc succinate, æinc amino acid chelate, zinc proteinate, zinc fumarate, zinc aspartate, zinc ascorbate, and zinc glycerophosphate. Most preferably, however, the dosage of zinc is about 15 mg as zinc oxide.
Manganese is a trace mineral essential to enzyme systems involved in bone development, insulin production as well as other enzyme systems. It is also required for the synthesis of cartilage mucopolysaccharides. Preferably, the manganese dosage is from about 0.5 to about 5 mg as manganese gluconate, manganese acetate, manganese carbonate, manganese chloride, manganese dioxide, manganese hypophosphite, manganese iodide, manganese silicate, manganese sulfate, manganese picolinate, manganese glycerophosphate, manganese lactate, manganese amino acid chelate, manganese proteinate, manganese ascorbate, manganese aspartate, manganese citrate, manganese fumarate, . . : ~ . - .
.. . . .- - . ....................... . - .
. - , , . . , . - , .
-. - . . ~. - -Z~ 7 - 20 -and manganese glycinate. More preferably, the manganese dosage i~ about 2.5 mg as manganese gluconate.
Selenium helps maintain proper immune system function.
It is an essential component of glutathione peroxidase, and as an antioxidant helps protect cells from free radical damage and toxic effects of certain chemicals.
Deficiencies are linked with increased risk of various cancers, along with increased risk of stroke, angina and heart attack. Selenium appears to work synergistically with several vitamins, minerals and antioxidants to lower cancer rates and to increase longevity. Preferably, the dosage of selenium included is from about 2 mcg to about l00 mcg as sodium selenate, selenous acid, potassium selenate, selenium oxide, selenomethionine, selenium yeast, selenium vegetable culture, selenium amino acid chelate, selenium proteinate, selenium ascorbate, selenium aspartate, sodium selenite, sodium selenate, potassium selenite, selenocystine, magnesium potassium selenate, magnesium selenate, cupric selenate, cupric selenite, zinc selenate, zinc selenite, calcium selenate, calcium selenite, selenium picoli~ate, selenium glycinate, and selenium glycerophosphate. Nost preferably, however, the dosage of selenium is about 25 mcg as sodium selenate.
Omega-3 (EPA/DHA) are polyunsaturated fatty acids.
Increased dietary levels of polyunsaturated fatty acids reduces platelet aggregation and has been linked to a lower incidence of heart disease and cancer. Omega 3 fish oils, preferably having an EPA:DHA ratio of about 18:12, are included in the supplement of the present invention in a dosage of from about l0 to about l,000 mg, more preferably, however, the dosage is from about 50 to about 800 mg, and most preferably about 200 mg. The omega-3 fish oil is preferably included as microencapsulated omega-3 fish oils, Omega 3 fish oils, cod liver oil, salmon oil, microencapsulated salmon oil, emulsified cod liver oil, k 5 , ~7 ", ""~
emulsified salmon oil, eicosapentaenoic acid, docosahexenoic acid, emulsified eicosapentaenopic acid, emulsified docosahexaenoic acid, fish oil, EPA, max EPA
sardine oil, microencapsulated sardine oil, halibut oil, or microencapsulated halibut oil. Most preferably, however, the omega-3 fish oil is microencapsulated omega-3 fish oil.
Inositol plays a vital metabolic role at the cellular level. Inositol is a bipotropic agent and plays a role in membrane and lipoprotein function. Inositol is preferably included in a dosage of from 5 to about lOOmg, and most preferably, about 50 mg.
According to one embodiment, the daily dietary multi-vitamin and mineral supplement of the present invention further includes para-aminobenzoic acid (PABA) in combination with the preferred amino acids and antioxidants of the present invention. PABA is an essential coenzyme in the metabolism of proteins and in the formation of red blood cells. PABA works synergistically with pantothenic acid. It has been reported that PABA may provide some pro-tection against hypertension and certain cancers. PABA is preferably included in the formulations of the present invention as para-aminobenzoic acid, potassium para-aminobenzoate, sodium para-aminobenzoate, magnesium para-aminobenzoate, calcium para-aminobenzoate. Most preferably, however, PABA is included as the acid in a dosage of from about lO to about lOO mg, and most preferably, about 40 mg.
Also, the following vitamins and minerals (Core IIIj, although not unique, are necessary and important in this f~ormulation because of their role in normal growth and general bodily needs. Once vitamins have crossed the intestinal walls, many function as co-enzymes essential to all cells. Because they work synergistically, or as a team, it is better to administer them together. A similar : . . . .
.
~ ,.
synergism is known for many of the minerals. They are as follows:
Folic Acid Vitamin B1 l vitamin B2 Niacinamide .vitamin B6 Vitamin B12 Vitamin D3 Biotin Ca Pantothenate Vitamin K~
Calcium Iodine Potassium Iron Magnesium Chromium Molybdenum Vanadium Silicon Boron ~-;
Compositions of the Core III formulations may be described as follows.
Folic Acid is an essential water-soluble vitamin. It is necessary for the synthesis of RNA and DNA, and therefore, vital in cell growth and division. Folic acid is important in red blood cell maturation and in other metabolic processes. The dose of folic acid included is from about 40 to about l,2000 mcg as folic acid, and most preferably, about 400 mcg. ;-Vitamin B1 (thiamine) is an essential water-soluble vita-min. It is important in the metabolism of carbohydrates and critical for the transmission of high-frequency impulses in the central nervous system as well as maintaining the integrity of the central nervous system.
Preferably, the dosage of vitamin B1 included is from about l to about 2 mg as thiamine hydrochloride, thiamine ~-mononitrate, thiamine chloride naphthalene-l, 5-disulfonic acid salt, thiamine triphosphoriate salt, thiamine : . : . .; , . . : , ~ .
% ~ ~ ~r~ ~
triphosphate ester, thiamine phosphoric acid ester phosphate salt, thiamine phosphoric acid ester chloride, and thiamine disulfide. Mos preferably, however, the dosage of vitamin B~ is about l.50 mg as thiamine hydrochloride.
Vitamin B2 (riboflavin) is an essential water-soluble vitamin which is required for the repair and growth of tissues as well as DNA synthesis. Vitamin B2 assists in metabolizing nutrients, e.g., proteins, fats and carbohydrates, and therefore, is critical in the release of energy. Preferably, the dosage of vitamin B2 is from about from 170 mcg to about 2 mg as riboflavin, riboflavin tetrabutyrate, riboflavin 5' phosphate sodium, and riboflavin monodiethanolamine salt dihydrate. Most preferably, however, the dosage of vitamin B2 is about l.75 mg as riboflavin.
Niacinamide is critical in the production of energy.
Niacinamide is water-soluble, and is an essential constituent of coenzymes I and II that occur in a wide variety of enzyme systems involved in the anaerobic oxidation of carbohydrates. Niacinamide is necessary for DNA formation, and important for the integrity of the central nervous system. Preferably, the dosage of niacinamide included is from about lO to about 30 mg as niacinamide, and most preferably, about 20 mg.
Vitamin B6 is a term commonly used for a group of three vitamins: pyridoxine, pyridoxal and pyridoxamine. They are important in protein and amino acid metabolism and help to regulate blood glucose levels. These vitamins are needed to synthesize hemoglobin and are important in the proper function of the central nervous system. The dosage of vitamin 88 is preferably from about 200 mcg to about 3 mg as pyridoxine hydrochloride, pyridoxal 5-phosphate, calcium .. . ' ~ : .-, .' , : , .
~ :: -~, .
2~ 24 -pyridoxine 5-phosphate, pyridoxal. Most preferably, however, the dosage of vitamin B6 is about 2 mg.
Vitamin B12 is an essential water soluble vitamin. It is critical for- bone growth, the integrity of the central nerve tissue, normal blood formation, and cell replication and DNA synthesis. Vitamin B1z deficiencies are related to certain anemias. Vitamin B12 is useful especially in the prevention of pernicious anemia. Preferably the dosage of Vitamin B12 included is from about 2 to about lO00 mcg as cyanocobalamin, cobalamin, Co-methylcyanocobalamin, zinc-vitamin B~2 - tannate, resin bound vitamin B12, and coenzyme Vitamin D3 is an oil-soluble vitamin. Vitamin D3 aids both the absorption of calcium and phosphorus. The primary role of vitamin D3 is the mineralization of bones and teeth and the regulation of blood calcium levels. Vitamin D3 is critical for the growth and differentiation of several tissues, and, it is believed, reduces the rate of certain cancers. The dosage of vitamin D3 included is preferably from about 40 to about 4,000 units as vitamin D3, water dispersable vitamin D3, water-soluble vitamin D3, and emulsified vitamin D3. Most preferably, however, the dose of vitamin D3 is about 600 units. ~
Biotin is a water-soluble vitamin essential in metabol- -ism. It is a coenzyme in the synthesis of fatty acids and amino acids. The dosage of biotin is preferably from lO to lO0 mcg as biotin, and most preferably, about 30 mcg. -Calcium pantothenate is a source of pantothenic acid, a water-soluble vitamin. Pantothenic acid is involved with the metabolism of proteins, fats and carbohydrates in the form of exoenzyme A, and is involved in the synthesis of sterols, hormones, porphyrins and acetylcholine. The ... . . . . . .
:, ., : -, . . : .
::.. .. - . : . : : - . . , : , . : : .
WO91tlll17 PCT/US91/00719 2 ~
- 25 - ; -dosage of calcium pantothenate is preferably from about 1 to about 50mg, and most preferably, about lOmg.
Vitamin K1 is an oil soluble vitamin which is necessary for the formation of prothrombinogen and other blood clotting factors. However, vitamin K-dependent protein in bone suggests a more complex role. Preferably, the dosage of Vitamin Kl is from about 3 to lOO mcg as trans isomer of vitamin K1, cis-trans isomers of vitamin Kl, emulsified trans isomer of vitamin K1, emulsified cis-trans isomers of vitamin K1, water soluble trans vitamin K1, water soluble cis-trans isomer of vitamin K1, vitamin K1 oxide, trans vitamin K1 oxide, emulsified cis-trans vitamin Kl oxide, water soluble trans vitamin Kl, water soluble cis-trans vitamin K1 oxide, vitamin K2 (2-methyl -3- all trans-polyprenyl-1, 4 napthoquinone) and those compounds of vitamin K2 which may possess side chains varying in length from C5 (n=1) to C6s (n=13), water soluble vitamin K2 and water soluble compounds of compounds of K2 which may possess side chains varying in length from C5 (n=1) to C65 (n=13), vitamin K5, dihydrovitamin K1, diphosphate ( ol, o4 diphosphoric acid) disodium salt of dihydrovitamin K1, tetrasodium salt of dihydrovitamin K1, tetrapotassium salt of dihydrovitamin K1, diphosphate ( ol, o4 - diphosphoric acid) dipotassium salt of dihydrovitamin K1, vitamin K6, vitamin K~, vitamin K~ hydrochloride, vitamin K5 (II), emulsified vitamin K5 (II), water soluble vitamin K5 (II).
Most preferably, however, the dose of vitamin K1 is about 25 mcg.
Calcium is involved with the transmission of nerve impulses, muscle contraction and relaxation, blood clotting, structure and function of cell membranes and B12 absorption. Dietary deficiencies are common and have been ~5 associated with accelerated bone loss resulting in alveolar bone loss and accompanying oral health problems, ",,~..... . - - - , , - . , .............. , , , , . , - . . . .
. : : .. ` . : : : - : -, ~:
. 2~ 26 -osteoporosis and hypertension. Calcium may also protect against certain type of cancer such as colon cancer Preferably, the calcium dosage included is from about 40 to about l,O00 mg as dicalcium phosphate dihydrate, dicalcium phosphate, monobasic calcium phosphate, tricalcium phosphate, calcium carbonate, calcium chloride, calcium citrate, calcium fluoride, calcium gluconate, calcium glycerophosphate, calcium hydroxide, calcium lactate, calcium levulinate, calcium sulfate, calcium succinate, calcium ascorbate, calcium fumarate, calcium lysinate, calcium malate, calcium aspartate, calcium amino acid chelate, calcium caseinate, calcium proteinate, calcium picolinate, calcium aspartate, calcium alpha ketoglutarate, calcium caseinate, calcium hydroxide, bone meal, oyster shell, calcium glycerophosphate, calcium hypophosphite, calcium ferrous citrate, calcium formate, calcium hypochlorite, calcium methionate, calcium biphosphate, calcium stearate, calcium tartrate, hydroxyapatite, dolomite, calcium sulfate dihydrate, calcium sulfate hemihydrate, dicalcium phosphate dihydrate, calcium acetate, calcium pyrophosphate, calcium gycinate. More preferable sources of calcium include calcium citrate, calcium carbonate, which act as free radical scavengers, calcium pantothenate, and dicalcium phosphate dihydrate.
Dicalcium phosphate dihydrate is source of calcium and phosphorus which functions in almost all aspects of metabolism, and also aids in the manufacturing (tableting) process.
Iodine is essential for proper thyroid functioning, and therefore, the regulation of the basal metabolic rate. The dosage of iodine included is from about 5 to 500 mcg as potassium iodide, sodium iodide, iodinated glycerol, kelp, Atlantic kelp, Pacific kelp, iodine-resublimed, potassium iodate, ferrous iodide, magnesium iodide, manganese iodide, iodine picolinate, iodine aspartate, iodine ,.. ,.. ~.. ,, ,., .. , , ~ - ................. , , ~ ,. . . .
.. . . . .. .
WO 9 1 /1 1 1 17 2~ - h5~ PCT/US9l/00719 2 7 ; . ` L . ' ' glycerophosphate. Most preferably, however, the dosage is about 150 mcg as potassium iodide.
Potassium is a major intracellular electrolyte.
Potassium aids in the transmission of nerve impulses, the release of insulin, and the proper functioning of digestive enzymes. Potassium works with sodium to maintain the balance of body fluids. Preferably, the dosage of 10 to about 1000 mg potassium is from about as potassium chloride, potassium acetate, potassium bicarbonate, potassium carbonate, potassium citrate, potassium gluconate, potassium glycerophosphate, potassium hydroxide, potassium nitrate, dipotassium phosphate, potassium dihydrogen phosphate, tripotassium phosphate, potassium sorbate, potassium sulfate, potassium proteinate, potassium amino acid chelate, potassium fumarate, potassium alpha ketoglutarate, potassium malate, potassium ascorbate, potassium succinate, potassium aspartate, potassium/magnesium aspartate, or potassium picolinate.
- Iron is an essential mineral and is needed to transport oxygen to the tissues throughout the body via hemoglobin and myoglobin. Iron is involved in the catalysis of many oxidative reactions within cells and is necessary for the proper functioning of many biochemical reactions. Iron plays a role in final steps of energy metabolism. Iron deficiencies are widespread, especially among women and children. Preferably, the dosage of iron included is from about 2 to about 50 mg as ferrous fumarate, ferrous carbonate mass, ferrous carbonate saccharated, ferrous chloride, ferrous citrate, ferrous gluconate, ferrous iodide, ferrous lactate, ferrous oxide, ferrous succinate, ferrous sulfate,- ferrous ascorbate, iron amino acid chelate, ferrous aspartate, ferrous peptonate, iron 3S proteinate, iron chloride, iron reduced, iron oxide saccharated, ferric glycerophosphate, and iron picolinate.
.. .
:.. ::: :
2~ ~,~7 - 28 -Most preferred, however, the dosage of iron is about 18 mg as iron gluconate.
Magnesium is a mineral essential for every biological S process including glucose metabolism, protein and nucleic acid synthesis, electrical balance of cells, and the trans-mission of nerve impulses. Magnesium effects the function and structure integrity and contractions of the heart and all other muscles. Dietary deficiencies are widespread.
Deficiencies have been linked to cardiovascular diseases.
Preferably, the dosage of magnesium included is from about 10 to about 500 mg as magnesium oxide, magnesium benzoate, magnesium carbonate hydroxide, magnesium chloride magnesium citrate, di-basic magnesium citrate, magnesium formate, magnesium hydroxide, magnesium iodide, magnesium lactate, magnesium peroxide, magnesium hydrogenphosphate, trimagnesium phosphate, magnesium silicate, magnesium stearate, magnesium sulfate, magnesium carbonate, magnesium gluconate, magnesium glycerophosphate, magnesium trisilicate, magnesium nicotinate, magnesium malate, magnesium amino acid chelate, magnesium picolinate, magnesium proteinate, magnesium lysinate, magnesium alpha ketoglutarate, and magnesium phosphinate hexahydrate. Most preferably, however, the dosage of magnesium is about 100 mg as magnesium oxide.
Chromium is a cofactor for insulin. Chromium is in-volved in carbohydrate metabolism, especially the utiliza-tion of glucose. Low chromium has been linked to diabetes and hypoglycemia. Low chromium has also been associated with heart disease. Chromium deficiencies are widespread.
Preferably, the dosage of chromium included is from about 2 to about 50 mcg as chromium ~+3) chloride, chromic acetate, chromic carbonate, chromic formate, chromic hydroxide, chromic nitrate, chromic oxide, chromic phosphate, chromic potassium sulfate, chromic sulfate, chromic picolinate, chromium polynicotinate, chromium ' ', ' . ' '`. . , ,, ' ' WO 91/11117 2~ PCT/US91/00719 ~ . r 2 9 ~ ~. . J.~
soured yeast, chromium vegetable culture, chromium amino - acid cheIated, chromium proteinate, chromium aspartate, chromium ascorbate, chromium GTF yeast, chromium glycinate, and chromium glycerophosphate. Most preferably, the dosage of chromium is about 25 mcg as chromium (+3) chloride.
Molybdenum is considered to be an essential trace mineral. Molybdenum plays a role in iron metabolism.
Preferably, the dosage of molybdenum included is from about 2 mcg to lO0 mcg as sodium molybdate, molybdenum amino acid chelate, molybdenum ascorbate, molybdenum yeast, molybdenum vegetable culture, molybdenum disulfide, molybdenum sesquioxide, molybdenum trioxide, sodium phosphomolybdate, molybdenum picolinate, molybdenum glycinate, and molybdenum glycerophosphate. Most preferably, however, the dosage of molybdenum is about 25 mcg as sodium molybdate.
Vanadium is a trace mineral found in the diet. Possible biochemical and physiological functions for vanadium have been suggested as including lipid metabolism, glucose metabolism, bone, and tooth metabolism. Vanadium may serve a catalytic function or may be an enzyme cofactor.
Preferably, the dosage of vanadium included is from about 2 mcg to about 100 mcg as sodium metavanadate, vanadium aspartate, vanadium amino acid chelate, vanadium proteinate, vanadium yeast, vanadium vegetable culture, potassium metavanadate, calcium vanadate, magnesium vanadate, ammonium metavanadate, vanadyl sulfate, oxytartarovanadate, vanadium picolinate, vanadium glycinate, and vanadium glycerophosphate.
.
Silicon functions as a biologic cross-linking agent that contributes to the structure and resilience of connective tissues, collagen, elastin and mucopolysaccharide. Silicon may be required for bone and cartilage collagen biosynthesis and is apparently involved in bone calcification. Preferably, the dosage of silicon included .,u.~...... , , , , ,, , ~ , , - , ~ , , ' -.. :
2~ ;.,7 is from about 2 mcg to about 50 mcg as sodium metasilicate, silica amino acid chelate, silicon proteinate, silicon plant source, silicon vegetable culture, silicon source trachea, silicon source tendon, silicon source aorta, silicon source mucopolysaccharide, silicon source pectin, silicon source alginic acid, silicic acid, silanolate, silicon dioxide, and silica. More preferably, the dosage of silicon is about 10 mcg as sodium metasilicate.
Findings suggest that boron influences the metabolism of calcium, phosphorus, magnesium and cholecalciferol. Boron may also be involved in the functional efficiency of membranes. Preferably, the dosage of boron included is from about dosage 500 mcg to about 2000 mcg as calcium borogluconate, magnesium borogluconate, sodium borate, boric acid, potassium borate, sodium metaborage, boron proteinate, boron amino acid chelate, glyceroborate, magnesium perborate, sodium perborate, calcium perborate, and potassium perborate. Most preferably, however, the dosage of boron is about 1 mg as calcium borogluconate.
With regard to the vitamins and minerals included in the inventive formulation, each (with the possible exception of vitamin A, calcium, magnesium and biotin) is included in an amount equal to or greater than the minimum daily requirement in man. Further, it is preferred that the vitamins and minerals included in the inventive formulation are similar to those included in the multi-vitamin and mineral preparations Centrum0 or One-A-Day0 (as shown in Table 3).
WO 91/11117 2~ 7 PCI`/US91/00719 . .
,, , . ., !. ~, . CENTRUM~ ONE-A-DAY
Vitamin Amount %USRDA Vitamin Amount ~USRDA
Vitamin A 5000 I.U. 100% Vitamin A 5000 I.U. 100%
(as Acetate . ~a~ Beta & Beta Carotene) carotens) Vitamin A 1500 I.U. 3C%
(a~ Acetate) Vitamin E 30 I.U. 100% Vltamin E 30 I.U. 10 (a~ DL-Alpha Tocopheryl Acetate) Vitamin C 60mg 100% Vitamin C 60mg 10~
(a~ Ascorbic Acid) ~:
Folic Acid 400 mcg 100~ Thiamine(Bl) 1.5mg 10~
Vitamin 81 1.5mg100% Riboflavin(B2) L~g 100%
(as Thiamine Mononitrate) -Vitamin B2 1.7mg100% Niacin 20mg 100%
(as Riboflavin) Niacinamide 20mg looe Vitamin D 400 I.U. 100% :.:
vitamin B6 2mg 100% Vitamin B6 2mg 100%
(ac Pyridoxine Hydrochloride) Vitamin B12 6mcg 100% Folic Acid 0.4mg 10 ~as Cyanocobalamin) Vitamin D 400 I.~. 100% vitamin Bl2 6mcg 10 Biotin 30mcg100% Biotin 30mcg 10%
Pantothenic Acid 10mg 100% Pantothenic 10mg 100%
Acid Calcium 162mg 16% Iron 18mg 10D%
(a~ Dibasic (elemental) Calcium Phosphate) Mineral Amount%USRDA Mineral Amount %USRDA
Pho~phorus 125mg 13% Calcium 130mg 13%
(as Dibasic Calcium Pho~phate) Iodine 150mcg100% Phocphorun 100mg 10%
~an Potacsium Iodine) Iron 18mg 100% Iodine 150mcg 10 (a~ Ferrou~ Fumarate) W091/11117 PCI`/US91/W7~
2~ ,7 Magne~ium lOOmg 25% Magneuium lOOmg 25%
(a~ Magne~ium Oxide) . .
Copper 2mg 100% Copper 2mg 10(as Cupric Oxide) Zinc 15mg 100% Zinc 15mg 10~ , (a~ Zinc OxLde) Mangane~e 2.5mg * Chromium lOmcg Pota~ium 40mg ~ Selenium lOmcg * `~
(as Potas~ium Chloride) Chloride 36.3mg * Molybdenum. lOmcg *
(as Potas~ium Chloride) Chromium 25mcg ~ Mangane~e 2.5mg *
(as Chromium Chloride) Molybdenum 25mcg ~ Pota~sium 37.5mg *
(a~ Sodium Molybdate) Selenium 25mcg ~ Chloride 34mg *
(a~ Sodium Selenate) Vitamin ~1 25mcg *
(a~ Phytonadione) Nickel Smcg *
(a~ Nic~el Sulfate) wo 91/11117 2~ PCT/US91/00719 f-33 ~ i. D ~ ' Mineral Amount ~USRDA Mineral Amount %USRDA
Tin lOmcg ~ .
(aQ Stannous Chloride) Silicon lOmcg *
(as Sodium Meta~ilicate) Vanadium lOmcg ~as Sodium Metavanadate) *No U.S. RDA establi~hed It is known that certain amino acids are essential for proper cellular function. However, it has been suggested by researchers that select amino acids provide some protection against cancer, and may, in fact, act synergistically with the preferred antioxidants of the present invention to protect against cancer. Thus, it is one important aspect of the present invention to provide a daily dietary multi-vitamin and mineral supplement including antioxidants and select amino acids. According to one embodiment of the invention, the preferred antioxidants are selected from the group consisting of BHT, BHA, propyl gallate, and sodium benzoate, and the preferred amino acids or analogs are selected from the group consisting of glutathione, cysteine, methionine, glutamine, and taurine.
Accordingly, one preferred embodiment of the present invention provides a daily dietary multi-vitamin and mineral supplement including, in combination:
(a) from about lO to about 300 mg of BHT;
tb) from about lO to about 300 mg of BHA;
(c) from about l to about 300 mg of sodium benzoate;
and (d) from about lO to about 300 mg of propyl gallate.
(e) from about l to about 20 mg of glutathione;
(f) from about 5 to about lO0 mg of cysteine;
(g) from about l to about 20 mg of methionine;
, WO91/111~7 ' ' PCT/US91/00719 2~7 '' ~7 ~ . ~
- 34 - '~
~ (h) from about l to about 20 mg of glutamine;
,:' (i) from about 2 to about 200 mg of bioflavonoids;
(j) from about l0 to 500 mg of potassium sorbate/sorbic acid; .:
(k) from about l to about 20 mg of taurine;
~l) from about 5,to 500 units of catalase as a food concentrate; and :
(l) from about 20 to about 500 units of SOD, as a food concentrate.
More preferably, however, the supplement includes:
(a) about 50 mg of BHT; ..
(b) about 50 mg of BHA; .
(c) about 4 mg of sodium benzoate; and (d) about 50 mg of propyl gallate.
(e) about l0 mg of reduced L-glutathione;
(f) about 50 mg of L-cysteine HCl; ,' (g) about l0 mg of DL-methionine;
(h) about l0 mg of DL-glutamine; and ' (i) about l00 mg of biofl,avonoids; - .. ~
(j) about 200 mg of potassium sorbate/sorbic acid; ~;
(k) about l0 mg of taurine; .,~
(l) about 150 units of catalase as a foo.d concentrate; and ~' (m) about 150 units of SOD as a food concentrate. .~
2~ :
In addition to the antioxidants and amino acids described above, several other ingredients may be included in the formulations of the invention, including:
(a) omega-3 fish oil;
(b) para-aminobenzoic acid (PABA); and .
(c) inositol.
'. -It has been demonstrated that several vitamins and minerals act synerg~stically in combination with several of the preferred antioxidants and amino acids of the ~,;
invention; therefore, it is an important aspect of the ~:.
present invention to provide formulation including these . '~
-.' ' ` , .: : - ;- . .
wo 91/11117 2~ ~ 5~ PCT/US91/00719 ... . . .
vitamins and minerals in appropriate amounts. Accordingly, a preferred embodiment of the present invention provides a daily dietary multi-vitamin and mineral tablet including, in combination:
(a) from about 10 to about 300 mg of BHT;
(b) from about lO to about 300 mg of BHA;
(c) from about 1 to about 300 mg of sodium benzoate;
(d) from about 10 to about 300 mg of propyl gallate.
(e) from about 1 to about 20 mg of glutathione;
( f ) from about 5 to about lO0 mg of cysteine;
(g) from about 1 to about 20 mg of methionine;
(h) from about 1 to about 20 mg of glutamine;
(i) from about 1 to about 20 mg of taurine;
(j) from about 1000 to about 3000 i.u. of vitamin A;
lS (k) from about 2500 to about 7500 i.u. of beta carotene;
(l) from about lO to about 100 i.u. of vitamin E;
(m) from about 10 to about 1000 mg Ca ascorbate; and (n) from about 10 to about 500 mg potassium sorbate or sorbic acid.
More preferably, however, the supplement includes:
(a) about 50 mg of BHT;
(b) about 50 mg of BHA;
(c) about 4 mg of sodium benzoate; and (d) about 50 mg of propyl gallate.
(e) about 10 mg of reduced L-glutathione;
(f) about 50 mg of L-cysteine HCl;
(g) about 10 mg of DL-methionine;
(h) about 10 mg of DL-glutamine;
(i) about 10 mg of taurine;
(j) about 2000 i.u. of vitamin A acetate;
(k) about 5000 i.u. of beta carotene;
(l) about 100 i.u. of vitamin E, DL alpha tocopheryl acetate;
(m) about 250 mg calcium ascorbate; and (n) about 200 mg of potassium sorbate or sorbic acid.
- .
:' ' .: ':,. ' :''' ' - . , ~ . , :
: ~' " , : . ' `, ~ .`;' ', ' ', ' ,-:' . ' .. : ''. ' .', ' ' -.. . . . . . .
WO91/11117 ~ PCI~U591/U071 ~ ~
2~ 36 -The inventive supplement includes many vitamins and minerals which are commonly used in commercially available , -multi-vitamin and mineral preparations. Preferably, the supplement of the present invention includes the following vitamins and minerals in an amount equal to or greater than the minimum daily requirement in man: ' (a) vitamin C;
(b) folic acid;
(c) vitamin Bl; :
(d) vitamin B2;
(e) niacinamide;
(f) vitamin B6;
(g) vitamin B~2;
(h) vitamin D3;
(i) biotin; -;~
(j) pantothenic acid;
(k) vitamin K~
(1) calcium;
. (m) iodine;
(n) potassium;
(o) iron;
(p) magnesium;
(q) copper;
(r) zinc;
(s) manganese; ~`
(t) chromium;
(u) molybdenum;
(v) selenium;
(w) vanadium;
(x) silicon; and (y) boron.
~ The formulations of the present invention contain a . number of vitamins and minerals similar to other multivi$a-min formulations, e.g, Centrum~. However, the formulation ~ --- ... .. . " ., ., . . , ~ . . , : -:: - . . . .
WO91/11117 2~ PCT/US91/00719 ,~ ~
of the present invention provides those vitamins and miner-als in amounts which better reflect the scientific data concerning these agents. For example, the amount of vitamin A included in the present invention is less than in other available formulations because it can be toxic to older people. Further, the amount of beta-carotene included is greater because it is nontoxic and provides improved benefits. For the above reasons the vitamins and minerals included in the present invention offer a broader base of vitamins a~d minerals than presently available in the industry; thus, providing the public with a comprehensive multivitamin useful in the prevention of heart disease and cancer.
According to one preferred embodiment, the vitamins and minerals included in the inventive formulation includes:
VITAMINS
(a) Vitamin A acetate from about lO00 to about 3000iu; (b) Beta carotene from about 3000 to about 6000iu;
(c) Vitamin E, DL alpha tocopheryl acetate from about 20 to about 40 iu;
(d) Calcium ascorbate from about 200 to about 400mg;
(e) Folic acid from about 200 to about 600mcg;
(f) Vitamin Bl from about l.0 to about 2mg;
(g) Vitamin B2 from about l.5 to about 2mg (h) Niacinamide from about lO to about 30mg;
(i) Vitamin B6 from about l to about 3mg;
(j) Vitamin B~2 from about 4 to about 8mcg;
(k) Vitamin D3 from about 400 to about 800iu;
(l) Biotin from about 20 to about 40mcg;
(m) Calcium pantothenate from about 5 to about 15mg;
and (n) Vitamin Kl from about 15 to about 35mcg.
- ~ . : . . . ,- - -. . . .
,, , - - -: . ., , . ~ - . ~ . .
:, :.: , . - - . ,, , ~, . ., ~ , i. ~ . .
W09ltllll7 PCr/US91/00719 2~ i~;~ 7 -- 38 MINERALS
(a) dicalcium phosphate from about 50 to about 150 mg;
(b) potassium iodide sufficient to supply from about 100 to about 150 mcg of iodine;
(c) potassium chloride sufficient to supply from ~ :
about 20 to about 60mg of potassium; .
(d) ferrous fumarate sufficient to supply from about 16 to about 30mg of iron; ~.
(e) magnesium oxide sufficient to supply from 75 to about 12Omg of magnesium;
(f) copper oxide sufficient to supply from about 1 to ~:
about 3mg of copper;
(h) zinc oxide sufficient to supply from about 10 to about 20mg of zinc;
(i) manganese gluconate sufficient to supply from about 1 to about 3mg of manganese;
(j) chromium (+3)chloride sufficient to supply from about 15 to about 35mcg of chromium;
(k~ sodium molybdate sufficient to supply from about 15 to about 35 mcg of molybdenum;
(l) sodium selenate sufficient to supply from about 15 to about 35mcg of selenium;
(m) sodium metavanadate sufficient to supply from about to about 15mcg of vanadium;
(n) sodium metasilicate sufficient to supply from about 5 to about 15mcg of silicon; and -~
(o) boron from about 1 to about 3mg. ~
~ ':
It should be noted, however, that other vitamins and minerals not listed above may be added to the formulations of the present invention without departing from the spirit of the present invention. ~ :
. .
However, according to the most preferred embodiment, the vitamins and minerals of the present invention include~
2~ 5~7 . ., ~,~, VITAMINS
(a) about 2000 i.u. of vitamin A acetate;
(b) about 5000 i.u. of beta carotene; ~:-(c) about 30 i.u. of vitamin E, DL alpha tocopheryl acetate;
(d) about 250mg of calcium ascorbate;
(e) about 400mcg of folic acid;
(f) about 1.5mg of vitamin B~
(g) about 1.75mg of vitamin B2;
(h) about 20mg of niacinamide; :.
(i) about 2mg of vitamin B6;
(j) about 6mcg of vitamin B12;
(k) about 6bo i.u. of vitamin D3; -::
(l) about 30mg of biotin; '~ --(m) about lOmg of calcium pantothenate; and ;
(n) about 25mcg of vitamin Kl. ~:
MINERALS :
_ _ .
(a) about lOOmg of dicalcium phosphate; ::
(b) potassium iodide sufficient to supply about 125mg :
iodine;
(c) potassium chloride sufficient to supply about :~ .
40mg of potassium;
(d) ferrous fumarate sufficient to supply about 20mg -.
of iron;
(e) magnesium oxide sufficient to supply about lOOmg of magnesium;
(f) copper oxide sufficient to supply about 2mg of copper; ~:
(h) zinc oxide sufficient to supply about 15mg of zinc;
(i) manganese gluconate sufficient to supply about 2mg of manganese;
(j) chromium (+3)chloride sufficient to supply about :
25mcg of chromium; :~
z~7 ~ 5~7 40 (k) sodium molybdate sufficient to suppIy about 25mcg of molybdenum;
(l) sodium selenate sufficient to supply about 25mcg of selenium;
(m) sodium metavanadate sufficient to supply about lOmcg of vanadium;
(n) sodium metasilicate sufficient to supply about lOmcg of silicon; and (o) about 2mg of boron.
The protective agents included in the inventive formulations are either already approved by the FDA or generally regarded as safe (GRAS) by the FDA or are generally thought to be safe by scientific experts. These agents include antioxidants, amino acids, and enzymes, which have been shown to be effective in preventing the induction of cancer and cardiovascular disorders as well as extending the life span of experimental animals. Further, a number of the ingredients have been shown to act synergistically with other agents in the formulation. This combined effect should increase their protective effects.
For example, selenium and vitamin E work synergistically against the induction of breast cancer. Further, in a number of studies, BHA when given with vitamin A, beta-carotene and vitamin E was shown to provide a protection against cancer. Accordingly, the present invention is directed to a multi-vitamin dietary supplement formulation, and methods for producing and administering the same to an individual in need thereof. It is believed that the present invention provides a formulation which is cardio-and cancer-protective.
A further aspect of the present invention is directed to a method for producing the formulations of the present invention. Preferably, the formulation is tableted, and most preferably, the formulation is tableted as a sustained release tablet. The sustained release tablets of the p~. ,~. , . . . . . , . . ~.
-. :- -. . ~ . .
. : . : . :.: . . . . :
WO91/11117 PCT/~S91/00719 - 41 - : ~
present invention are intended to provide for the extended action of the ingredients from a single dose. Thus, the sustained released tablet is a convenient dosage form by virtue of eliminating the necessity for dosage several times during the day. Moreover, therapeutic benefits may also be obtained by the sustained release of the active ingredients of the inventive formulation. It is believed desireable that the sustained release dosage form of the present invention will provide a slow and constant supply of antioxidants, amino acids, and other beneficial dietary supplements which will provide protection against cancer and cardiovascular disease throughout the day.
In order to stabilize the preparations of the present lS invention, it has been determined that several of the more reactive constituents are preferably microencapsulated.
The microencapsulation of select constituents prevents those constituents from reacting with other ingredients if left unchecked, which would shorten the shelf life of a commercial product embodying the inventive formulation.
According to one embodiment, the preferred sulfur-containing amino acids and the polyunsaturated acids are microencapsulated. More specifically, glutathione, cysteine, and omega-3 fish oil are preferably microencapsulated when included in the invented formulation.
According to one preferred embodiment, hydroxypropyl methylcellulose is used as a pharmaceutical adjunct which provides a sustained release of the active constituents of the tablet. According to this preferred embodiment, based upon the physical parameters involved in formation of a tablet which is determined by the nature of the ingredients (compressibility, adhesion of particles, etc.), up to 20%
of the dry weight could be required for hydroxypropyl methylcellulose to ensure proper time release tablet.
Thus, according to one embodiment, a total formulation . ~, . : ~ . , . - :,. .: .
W~91/11117 PCT/US91/00719 z~ ~5,, ~ - 42 -weight range, including time released material, would have a weight range of from about 4090 mg to about 3526 mg.
Because of the bulk of the formulation, the formulation is preferably produced and administered as 1-3 tablets daily.
, The following examples are presented to describe specific preferred embodiments and utilities of the present invention and are not meant to limit the present invention unless otherwise stated in the claims appended hereto.
EXAMPLES
In vitro disintearation characteristics A comparison was made between the relative disintegrations of Centrum tablets and the sustained release tablets of the present invention.
As a measurement of disintegration, the release of four different vitamins, potassium, vitamin C, niacinamide, and pyridoxine was measured. The results, summarized in Figs. 1-6, show that the sustained release tablet of the present invention provides for uniform disintegration over at least seven hours.
As a general procedure, gastric and intestinal juices were prepared according to the United States Pharmacopeia XVIII. The dissolution tests were conducted using the apparatus specified for such procedures in the National Formulary XIII. The apparatus generally consisted of a horizontal rotating shaft to which was attached clamps for holding round cylinders approximately 150mm long and having a diameter of approximately 30 mm wherein the tablets were contained. The apparatus then submerges the tablets in the appropriate dissolution fluid. The temperature of the dissolutions fluid was maintained at 37+ 2 C throughout the study. Eight tablets were used to generate the dissolution .: : . : ~ . ~ : .: . -: : .
WO91~11117 PCT/US91/00719 1 2~ ~ ~ 43 _ ,~
data. Six Centrum (UDC0005-4239-13 Lederle Laboratories Division American Cyanamid Company) and two sustained release tablets of the present i~vention, which were prepared as follows.
The following shows the content and instructions for preparing a most preferred formulation (300,000 tablets 3 tablet/dose) of the present invention.
Weight Range Per Do~e ~dose = 1 dav su~lv) G _ vitamins 5.4 mgVitamin A acetate 2000 iu from 500,000 iu/gm beadlet~ with 35% overage 540 40.5 mgBeta carotene 5000 iu = 30 mg with 35% overage from 10% beadlets 405 231 mg Vitamin E DL alpha tocopheryl acetate 100 iu from 50% 2.1 mg finished material with 10% overage 23,100 300 mg Calcium ascorbate = 250 mg with 20% overage 30,000 mg Follc acid as 10% trit = 400 mcg/do~e with 25%
overage 500 1.73mg Vitamin Bl dose = 1.5 mg with 15~ overage173 1.87mg Vitamin B2 dose = 1.7 mg with 10% overage187 3022 mg Niacinamide dose = 20 mg with 10% overage2,200 2.67mg Vitamin B6 dose = 2 mg with 10% overage 267 0.75mg Vita~in B12 dose = 6 mcg from 1% trit on re~in with 25% overage 75 8.1 mg Vitamin D3 dose = 600 iu from 100,000 iu/gm with 35% overage 810 403.3 mg BiotLn do~e = 30 mcg from 1% trit with 10% overage 330 14 mg Calcium pantothenate dose = 10 mg with 30~ overage 1,400
3.4 mg Vitamin ~1 dose = 25 mcg from 1% trit with 35%
overage 340 100 mg Dicalcium phosphate dihydrate10,000 (use in granulations) S0 0.20mg Pota~ium iodide supplies 150 mcg iodine 20 76.3 mg Pota6~ium chloride supplies 40 mg pota~ium 7,630 155 mg Ferrous gluconate supplies 18 mg iron 15,550 166 mg Magnesium oxide supplies lO0 mg magne~ium16,660 WO9]/11117 PCr/US91/00719 ~` .
2~7~ 44 -2.503mg Copper oxide supplies 2 mg copper 250 18.75mg Zinc oxide supplies 15 mg zinc1,875 22.7 mg Manganese gluconate supplies 2.5 mg manganese 2,270 0.08mg Chromium (+3) chloride supplie~ 25 mcg chromium 8Z
0.06mg Sodium molybdate supplies 25 mcg molybdenum 63 0.06mg Sodium selenate supplies 25 mcg ~elenium 64 0.038mg S o d i u m metavanadate supplies 10 mcg vanadium 3.86 0.044mg S o d i u m metasilicate supplies 10 mcg silicon 4.45 22.3 mg Calcium borogluconate supplies 1 mg boron 2,230 100 mg Citrus bioflavonoids from 50~ material supplying 50 mg per dose 10,000
overage 340 100 mg Dicalcium phosphate dihydrate10,000 (use in granulations) S0 0.20mg Pota~ium iodide supplies 150 mcg iodine 20 76.3 mg Pota6~ium chloride supplies 40 mg pota~ium 7,630 155 mg Ferrous gluconate supplies 18 mg iron 15,550 166 mg Magnesium oxide supplies lO0 mg magne~ium16,660 WO9]/11117 PCr/US91/00719 ~` .
2~7~ 44 -2.503mg Copper oxide supplies 2 mg copper 250 18.75mg Zinc oxide supplies 15 mg zinc1,875 22.7 mg Manganese gluconate supplies 2.5 mg manganese 2,270 0.08mg Chromium (+3) chloride supplie~ 25 mcg chromium 8Z
0.06mg Sodium molybdate supplies 25 mcg molybdenum 63 0.06mg Sodium selenate supplies 25 mcg ~elenium 64 0.038mg S o d i u m metavanadate supplies 10 mcg vanadium 3.86 0.044mg S o d i u m metasilicate supplies 10 mcg silicon 4.45 22.3 mg Calcium borogluconate supplies 1 mg boron 2,230 100 mg Citrus bioflavonoids from 50~ material supplying 50 mg per dose 10,000
4 mg Sodium benzoate 25,000 250 mg Calcium carbonate 25,000 100 mg Calcium citrate 10,000 10 mg L-glutathione ~reduced) (microencapsulated) 2,500 50 mg L-cysteine HC1 (microencapsulated) 5,000 200 mg Potassium sorbate/sorbic acid 20,000 3540 mg PABA 4,000 50 mg BHA 5,000 50 mg 8BT 5,000 571 mg Omega 3 fish oils supplying 200 mg Omega 3 oils from microencapsulated material which is 35%
omega 3 having an EPA:DHA ratio of 18:12 57,100 4550 mg Inositol 5,000 150 mg Vegetable source SOD 200 units (mfu) Vegetable source catalase 200 units (bsu) 15,000 50 mg Propyl gallate 5,000 10 mg Taurine 1,000 10 mg DL methionine 1,000 10 mg L glutamine 1,000 hydroxypropylmethylcellulose (e.g. Methocel X, Dow Chem.)61,162 Magnesium Stearate 1,500 Total weight of ingredients = 376,102 Tablet Weight = 1.1667 grams . .. . .
WO 91/111l7 PCl`tUS9l/00719 2~
The KI was dissolved in 50 ml H20 with about 2000 gm of the dicalcium phosphate dihydrate. The mixture was dried at 120-F for 48 hours and then milled. The CrCl3 was also dissolved in 50 ml H20 with about 2000 gms dicalcium phosphate dihydrate. This mixture was also dried at 120`F
for about 48 hours and was then milled. The sodium molybdate was dissolved in 50 ml H2O with about 2000 gm of dicalcium phosphate dihydrate. The mixture was dried at 120`F for about 48 hours and then milled. The sodium selenate was dissolved in 50 ml H2O with 2000 gms dicalcium phosphate dihydrate and dried at 120-F for about 48 hours and then was milled. The sodium metasilicate was mixed with 2000 gms dicalcium phosphate dihydrate and added to the sodium metavandate which was dissolved in 50 ml H2O.
This mixture was then dried at 120-F for about 48 hours and then was milled. All of the above milled ingredients were then mixed.
All the remaining ingredients were weighed separately and added to a stainless steel ribbon blender and blended for 10 minutes. Tablets were then compressed on a rotary tablet press machine. Tablets weighed 1.2537 grams 1 2%.
The tablets were oblong measuring 0.75 inches (height) x 0.35 inches ~width) x 0.30 inches (depth). The tablets were produced at 4 tons pressing force per square inch. It was determined that these tablets disintegrated uniformly over an 8 hour period. The tablets are also suitable for an aqueous film coating, such as with riboflavin, in a conventional film coating pan.
: .
The dissolution data was collected at 1/2 hr, 1 and 1/2 hr, 2 and 1/2 hr, 3 and 1/2 hr, 4 and 1/2 hr, 5 and 1/2 hr, 6 and 1/2 hr, and 7 and 1/2 hr. Data for Centrum was obtained for 6 tablets under identical conditions.
However, the total dissolution occurred for Centrum at approximately 20 minutes. Therefore, Centrum was only 2 ~ ~r;~ 7 - 46 - _ observed in gastric test solution. This data is summarized in Fig. 1.
.
The release of potassium from the tablet of the present invention was monitored using a Perkin Elmer spectrophotometer. To do this monobase sodium phosphate was used in place of H2KPO4 in the intestinal liquid.
Replacement of H2KPO4 with H2NaPO~ allowed accurate measurement of potassium from the tablet without interferences.
Measurements of potassium were made at 766.5 lambda using atomic absorption. Results:
Time %K released during observed interval 0 - 1/2hr 11.54 lt2 - 2 1/2hr 14.61 1/2 - 2 1/2hr 14.61 2 1/2 - 3 1/2hr 14.61 3 1/2 - 4 1/2hr 13.15 4 1/2 - 5 1/2hr 13.15
omega 3 having an EPA:DHA ratio of 18:12 57,100 4550 mg Inositol 5,000 150 mg Vegetable source SOD 200 units (mfu) Vegetable source catalase 200 units (bsu) 15,000 50 mg Propyl gallate 5,000 10 mg Taurine 1,000 10 mg DL methionine 1,000 10 mg L glutamine 1,000 hydroxypropylmethylcellulose (e.g. Methocel X, Dow Chem.)61,162 Magnesium Stearate 1,500 Total weight of ingredients = 376,102 Tablet Weight = 1.1667 grams . .. . .
WO 91/111l7 PCl`tUS9l/00719 2~
The KI was dissolved in 50 ml H20 with about 2000 gm of the dicalcium phosphate dihydrate. The mixture was dried at 120-F for 48 hours and then milled. The CrCl3 was also dissolved in 50 ml H20 with about 2000 gms dicalcium phosphate dihydrate. This mixture was also dried at 120`F
for about 48 hours and was then milled. The sodium molybdate was dissolved in 50 ml H2O with about 2000 gm of dicalcium phosphate dihydrate. The mixture was dried at 120`F for about 48 hours and then milled. The sodium selenate was dissolved in 50 ml H2O with 2000 gms dicalcium phosphate dihydrate and dried at 120-F for about 48 hours and then was milled. The sodium metasilicate was mixed with 2000 gms dicalcium phosphate dihydrate and added to the sodium metavandate which was dissolved in 50 ml H2O.
This mixture was then dried at 120-F for about 48 hours and then was milled. All of the above milled ingredients were then mixed.
All the remaining ingredients were weighed separately and added to a stainless steel ribbon blender and blended for 10 minutes. Tablets were then compressed on a rotary tablet press machine. Tablets weighed 1.2537 grams 1 2%.
The tablets were oblong measuring 0.75 inches (height) x 0.35 inches ~width) x 0.30 inches (depth). The tablets were produced at 4 tons pressing force per square inch. It was determined that these tablets disintegrated uniformly over an 8 hour period. The tablets are also suitable for an aqueous film coating, such as with riboflavin, in a conventional film coating pan.
: .
The dissolution data was collected at 1/2 hr, 1 and 1/2 hr, 2 and 1/2 hr, 3 and 1/2 hr, 4 and 1/2 hr, 5 and 1/2 hr, 6 and 1/2 hr, and 7 and 1/2 hr. Data for Centrum was obtained for 6 tablets under identical conditions.
However, the total dissolution occurred for Centrum at approximately 20 minutes. Therefore, Centrum was only 2 ~ ~r;~ 7 - 46 - _ observed in gastric test solution. This data is summarized in Fig. 1.
.
The release of potassium from the tablet of the present invention was monitored using a Perkin Elmer spectrophotometer. To do this monobase sodium phosphate was used in place of H2KPO4 in the intestinal liquid.
Replacement of H2KPO4 with H2NaPO~ allowed accurate measurement of potassium from the tablet without interferences.
Measurements of potassium were made at 766.5 lambda using atomic absorption. Results:
Time %K released during observed interval 0 - 1/2hr 11.54 lt2 - 2 1/2hr 14.61 1/2 - 2 1/2hr 14.61 2 1/2 - 3 1/2hr 14.61 3 1/2 - 4 1/2hr 13.15 4 1/2 - 5 1/2hr 13.15
5 1/2 - 6 1/2hr 10.96
6 1/2 - 7 1/2hr 7.30 25To obtain interval values intestinal fluid was replaced hourly. The above data is summarized in Fig. 2.
Data for ascorbic acid, niacinamide, and pyridoxine HCl were generated using a Bausch and Lomb 30spectrophotometer (Model 21). The wavelengths used for analysis were: -245mm Ascorbic Acid 261mm Niacinamide 29imm Pyridoxine Samples were taken from 1/2hr, 1/2hr, 2 1/2hr, 3 1/2hr, 4 1/2hr, 5 1/2hr, 6 1/2hr, 7 1/2hr periods. ~his data is : . . ~ ~ : - , W091/~1117 PCTtUS9ltO0719 5~
, summarized in Figs. 3, 4, and 5 respectively. The data collected showed that the tablet of the present invention provided for the sustained release of the constituents of the inventive formulation.
While the invention is susceptible to various modifications and alternative forms, a specific embodiment thereof has been shown by way of example and therein was described in detail. It should be understood, however, that it is not intended to limit the invention to the particular forms disclosed, but on the contrary, the intention is to cover all modifications, equivalents, and alternatives falling within the spirit and scope of the invention as defined by the appended claims.
: . : . . . . . . .
Data for ascorbic acid, niacinamide, and pyridoxine HCl were generated using a Bausch and Lomb 30spectrophotometer (Model 21). The wavelengths used for analysis were: -245mm Ascorbic Acid 261mm Niacinamide 29imm Pyridoxine Samples were taken from 1/2hr, 1/2hr, 2 1/2hr, 3 1/2hr, 4 1/2hr, 5 1/2hr, 6 1/2hr, 7 1/2hr periods. ~his data is : . . ~ ~ : - , W091/~1117 PCTtUS9ltO0719 5~
, summarized in Figs. 3, 4, and 5 respectively. The data collected showed that the tablet of the present invention provided for the sustained release of the constituents of the inventive formulation.
While the invention is susceptible to various modifications and alternative forms, a specific embodiment thereof has been shown by way of example and therein was described in detail. It should be understood, however, that it is not intended to limit the invention to the particular forms disclosed, but on the contrary, the intention is to cover all modifications, equivalents, and alternatives falling within the spirit and scope of the invention as defined by the appended claims.
: . : . . . . . . .
Claims (73)
1. A daily dietary multivitamin and mineral supplement comprising:
bioflavonoids L-glutathione (reduced) L-cysteine Potassium sorbate/sorbic acid BHA
BHT
Propyl gallate Sodium benzoate Taurine D, L-Methionine L-glutamine SOD and catalase (preferably in food concentrate).
bioflavonoids L-glutathione (reduced) L-cysteine Potassium sorbate/sorbic acid BHA
BHT
Propyl gallate Sodium benzoate Taurine D, L-Methionine L-glutamine SOD and catalase (preferably in food concentrate).
2. The supplement of claim 1 further defined as including:
Vitamin A
B-carotene Vitamin E
Ca Ascorbate Copper Zinc Manganese, Selenium Omega-3 fish oil Inositol; and PABA
Vitamin A
B-carotene Vitamin E
Ca Ascorbate Copper Zinc Manganese, Selenium Omega-3 fish oil Inositol; and PABA
3. The supplement of claim 1 further defined as including:
Folic Acid Vitamin B1 Vitamin B2 Niacinamide Vitamin B6 Vitamin B12 Vitamin D3 Biotin Ca Pantothenate Vitamin K1 Calcium Iodine Potassium Iron Magnesium Chromium Molybdenum Vanadium Silicon and Boron.
Folic Acid Vitamin B1 Vitamin B2 Niacinamide Vitamin B6 Vitamin B12 Vitamin D3 Biotin Ca Pantothenate Vitamin K1 Calcium Iodine Potassium Iron Magnesium Chromium Molybdenum Vanadium Silicon and Boron.
4. A daily dietary supplement comprising:
bioflavonoids L-glutathione (reduced) Cysteine Potassium sorbate/sorbic acid BHA
BHT
Propyl gallate Sodium benzoate Taurine D L-Methionine L-glutamine SOD and catalase (preferably in food concentrate) Vitamin A
B-carotene Vitamin E
Ca Ascorbate Copper Zinc Manganese Selenium Omega 3 fish oil Inositol PABA
Folic Acid Vitamin B1 Vitamin B2 Niacinamide Vitamin B6 Vitamin B12 Vitamin D3 Biotin Ca Pantothenate Vitamin K1 Calcium Iodine Potassium Iron Magnesium Chromium Molybdenum Vanadium Silicon and Boron.
bioflavonoids L-glutathione (reduced) Cysteine Potassium sorbate/sorbic acid BHA
BHT
Propyl gallate Sodium benzoate Taurine D L-Methionine L-glutamine SOD and catalase (preferably in food concentrate) Vitamin A
B-carotene Vitamin E
Ca Ascorbate Copper Zinc Manganese Selenium Omega 3 fish oil Inositol PABA
Folic Acid Vitamin B1 Vitamin B2 Niacinamide Vitamin B6 Vitamin B12 Vitamin D3 Biotin Ca Pantothenate Vitamin K1 Calcium Iodine Potassium Iron Magnesium Chromium Molybdenum Vanadium Silicon and Boron.
5. A daily dietary multi-vitamin and mineral supplement for a human including from about 10 to about 300 mg of BHT.
6. A daily dietary multi-vitamin and mineral supplement for a human including about 50 mg of BHT.
7. A daily dietary multi-vitamin and mineral supplement for a human including from about 10 to about 300 mg of BHA.
8. A daily dietary multi-vitamin and mineral supplement for a human including from about 10 to about 300 mg of propyl gallate.
9. A daily dietary multi-vitamin and mineral supplement for a human including from about 1 to about 300 mg of sodium benzoate.
10. A daily dietary multi-vitamin and mineral supplement for a human including about 4 mg of sodium benzoate.
11. A daily dietary multi-vitamin and mineral supplement for a human including in combination:
from about 10 to about 300 mg of BHT;
from about 10 to about 300 mg of BHA;
from about 1 to about 300 mg of sodium benzoate; and from about 10 to about 300 mg of propyl gallate.
from about 10 to about 300 mg of BHT;
from about 10 to about 300 mg of BHA;
from about 1 to about 300 mg of sodium benzoate; and from about 10 to about 300 mg of propyl gallate.
12. The supplement of claim 11 wherein said supplement further includes in combination:
from about 1 to about 20 mg of glutathione;
from about 5 to about 100 mg of cysteine;
from about 1 to about 20 mg of methionine;
from about 1 to about 20 mg of glutamine; and from about 1 to about 20 mg of taurine;
from about 1 to about 20 mg of glutathione;
from about 5 to about 100 mg of cysteine;
from about 1 to about 20 mg of methionine;
from about 1 to about 20 mg of glutamine; and from about 1 to about 20 mg of taurine;
13. The supplement of claim 12 wherein said supplement further includes from about 10 to 100 mg of PABA.
14. The supplement of claim 12 wherein said supplement further includes from about 10 to about 1000 mg of polyunsaturated fatty acids having an EPA:DHA ratio of about 18:12.
15. The supplement of claim 12 wherein said supplement further includes from about 100 to about 300 i.u. of superoxide dismutase.
16. The supplement of claim 15 wherein said supplement further includes from about 100 to about 300 i.u. of catalase.
17. The supplement of claim 16 wherein the superoxide dismutase or catalase is from a food concentrate.
18. The supplement of claim 11 wherein said supplement includes from about 2 to about 200 mg of a bioflavonoid.
19. The supplement of claim 11 wherein said supplement further includes:
from about 1000 to about 3000 i.u. of vitamin A;
from about 2500 to about 7500 i.u. of beta carotene;
and from about 10 to about 100 i.u. of vitamin E.
from about 1000 to about 3000 i.u. of vitamin A;
from about 2500 to about 7500 i.u. of beta carotene;
and from about 10 to about 100 i.u. of vitamin E.
20. The supplement of claim 11 wherein said supplement further includes at least the minimum daily requirement in man of:
vitamin C;
folic acid;
vitamin B1;
vitamin B2;
niacinamide;
vitamin B6;
vitamin B12;
vitamin D3;
biotin;
pantothenic acid; and vitamin K1.
vitamin C;
folic acid;
vitamin B1;
vitamin B2;
niacinamide;
vitamin B6;
vitamin B12;
vitamin D3;
biotin;
pantothenic acid; and vitamin K1.
21. The supplement of claim 20 wherein said supplement further includes at least the daily requirement in man of a pharmaceutically acceptable mineral salt of:
calcium;
iodine;
potassium;
iron;
magnesium;
copper;
zinc;
manganese;
chromium;
molybdenum;
selenium;
(1) vanadium;
silicon; and boron.
calcium;
iodine;
potassium;
iron;
magnesium;
copper;
zinc;
manganese;
chromium;
molybdenum;
selenium;
(1) vanadium;
silicon; and boron.
22. The supplement of claim 23 wherein said supplement further includes from about 5 to about 100 mg of inositol.
23. A daily dietary multi-vitamin and mineral supplement for a human including about 50 mg of BHT.
24. A daily dietary multi-vitamin and mineral supplement for a human including about 50 mg of BHA.
25. A daily dietary multi-vitamin and mineral supplement for a human including about 50 mg propyl gallate.
26. A daily dietary multi-vitamin and mineral supplement for a human including about 4 mg of sodium benzoate.
27. A daily dietary multi-vitamin and mineral supplement for a human including in combination:
about 50 mg of BHT;
about 50 mg of BHA;
about 4 mg of sodium benzoate; and about 50 mg of propyl gallate.
about 50 mg of BHT;
about 50 mg of BHA;
about 4 mg of sodium benzoate; and about 50 mg of propyl gallate.
28. The dietary supplement of claim 28 wherein said supplement further includes in combination:
about 10 mg of reduced L-glutathione;
about 50 mg of L-cysteine HCl;
about 10 mg of L-methionine;
about 10 mg of L-glutamine; and about 10 mg of taurine;
about 10 mg of reduced L-glutathione;
about 50 mg of L-cysteine HCl;
about 10 mg of L-methionine;
about 10 mg of L-glutamine; and about 10 mg of taurine;
29. The dietary supplement of claim 27 which further includes from about 10 to 100 mg of PABA, and from about 5 to about 50 mg of calcium pantothenate.
30. The dietary supplement of claim 27 which further includes about 200 mg Omega-3 fish oil having an EPA:DHA
ratio of about 18:12.
ratio of about 18:12.
31. The dietary supplement of claim 27 wherein said supplement further includes about 150 i.u. of superoxide dismutase.
32. The dietary supplement of claim 31 wherein said supplement further includes about 150 i.u. of catalase.
33. The dietary supplement of claim 32 wherein the superoxide dismutase and catalase are from a food concentrate.
34. The dietary supplement of claim 27 wherein said supplement includes about 50 mg of a bioflavonoid.
35. The dietary supplement of claim 27 wherein said supplement further includes:
about 2000 i.u. of vitamin A acetate;
about 5000 i.u. of beta carotene;
about 100 i.u. of vitamin E, DL alpha tocopheryl acetate;
about 250 mg calcium ascorbate; and about 200 mg of potassium sorbate or sorbic acid.
about 2000 i.u. of vitamin A acetate;
about 5000 i.u. of beta carotene;
about 100 i.u. of vitamin E, DL alpha tocopheryl acetate;
about 250 mg calcium ascorbate; and about 200 mg of potassium sorbate or sorbic acid.
36. A daily dietary multi-vitamin and mineral supplement for a human including, in combination, about 50 mg of BHT, and about 2000 i.u. of vitamin A acetate.
37. A daily dietary multi-vitamin and mineral supplement for a human including, in combination, about 50 mg of BHT, and about 5000 i.u. of beta carotene.
38. A daily dietary multi-vitamin and mineral supplement for a human including, in combination:
at least one antioxidant selected from the group consisting of BHT, BHA, propyl gallate, and sodium benzoate;
vitamin A;
vitamin E; and beta carotene.
at least one antioxidant selected from the group consisting of BHT, BHA, propyl gallate, and sodium benzoate;
vitamin A;
vitamin E; and beta carotene.
39. The dietary supplement of claim 38 wherein said supplement further includes a pharmaceutically acceptable salt comprising selenium.
40. The dietary supplement of claim 38 wherein said supplement further includes, in combination, at least one amino acid selected from the group consisting of reduced L-glutathione, L-cysteine HCl, DL-methionine, L-glutamine, and taurine.
41. The dietary supplement of claims 21, 35, 38, or 40 wherein said supplement is prepared as a sustained release tablet.
42. A daily. dietary supplement formulated as an oral sustained release tablet including, in combination:
about 2000iu of vitamin A acetate;
about 5000iu of beta carotene;
about 30iu of vitamin E, DL alpha tocopheryl acetate;
about 250mg of calcium ascorbate;
about 400mcg of folic acid;
about 1.5mg of vitamin B,;
about 1.75mg of vitamin B2;
about 20mg of niacinamide;
about 2mg of vitamin B6;
about 6mcg of vitamin B12;
about 600iu of vitamin D3;
about 30mg of biotin;
about 10mg of calcium pantothenate; and about 25mcg of vitamin K1;
about 100mg of dicalcium phosphate;
potassium iodide sufficient to supply about 125mg iodine;
potassium chloride sufficient to supply about 40mg of potassium;
ferrous fumarate sufficient to supply about 20mg of iron;
magnesium oxide sufficient to supply about 100mg of magnesium;
copper oxide sufficient to supply about 2mg of copper;
zinc oxide sufficient to supply about 15mg of zinc;
manganese gluconate sufficient to supply about 2mg of manganese;
chromium (+3)chloride sufficient to supply about 25mcg of chromium;
sodium molybdate sufficient to supply about 25mcg of molybdenum;
sodium selenate sufficient to supply about 25mcg of selenium;
sodium metavanadate sufficient to supply about 10mcg of vanadium;
sodium metasilicate sufficient to supply about 10mcg of silicon; and about 2mg of boron;
about 4mg of sodium benzoate;
about 250mg of calcium carbonate;
about 100mg of calcium citrate;
about 200mg of potassium sorbate or sorbic acid;
about 40mg of PABA;
about 200mg of Omega-3 fish oil;
about 50mg of inositol;
about 200iu of superoxide dismutase from a food concentrate;
about 200iu of catalase from a food concentrate;
about 50mg of BHT;
about 50mg of BHA; and about 50mg of a bioflavonoid.
about 2000iu of vitamin A acetate;
about 5000iu of beta carotene;
about 30iu of vitamin E, DL alpha tocopheryl acetate;
about 250mg of calcium ascorbate;
about 400mcg of folic acid;
about 1.5mg of vitamin B,;
about 1.75mg of vitamin B2;
about 20mg of niacinamide;
about 2mg of vitamin B6;
about 6mcg of vitamin B12;
about 600iu of vitamin D3;
about 30mg of biotin;
about 10mg of calcium pantothenate; and about 25mcg of vitamin K1;
about 100mg of dicalcium phosphate;
potassium iodide sufficient to supply about 125mg iodine;
potassium chloride sufficient to supply about 40mg of potassium;
ferrous fumarate sufficient to supply about 20mg of iron;
magnesium oxide sufficient to supply about 100mg of magnesium;
copper oxide sufficient to supply about 2mg of copper;
zinc oxide sufficient to supply about 15mg of zinc;
manganese gluconate sufficient to supply about 2mg of manganese;
chromium (+3)chloride sufficient to supply about 25mcg of chromium;
sodium molybdate sufficient to supply about 25mcg of molybdenum;
sodium selenate sufficient to supply about 25mcg of selenium;
sodium metavanadate sufficient to supply about 10mcg of vanadium;
sodium metasilicate sufficient to supply about 10mcg of silicon; and about 2mg of boron;
about 4mg of sodium benzoate;
about 250mg of calcium carbonate;
about 100mg of calcium citrate;
about 200mg of potassium sorbate or sorbic acid;
about 40mg of PABA;
about 200mg of Omega-3 fish oil;
about 50mg of inositol;
about 200iu of superoxide dismutase from a food concentrate;
about 200iu of catalase from a food concentrate;
about 50mg of BHT;
about 50mg of BHA; and about 50mg of a bioflavonoid.
43. A method for preventing cancer in a human subject, the method including the step of administering daily an oral sustained release tablet including the dietary multi-vitamin and mineral supplement comprising from about 10 to about 300 mg of BHT.
44. A method for preventing cancer in a human subject, the method including the step of administering daily an oral sustained release tablet including the dietary multi-vitamin and mineral supplement comprising from about 10 to about 300 mg of BHA.
45. A method for preventing cancer in a human subject, the method including the step of administering daily an oral sustained release tablet including the dietary multi-vitamin and mineral supplement comprising from about 10 to about 300 mg of propyl gallate.
46. A method for preventing cancer in a human subject, the method including the step of administering daily an oral sustained release tablet to an individual including in combination:
from about 10 to about 300 mg of BHT;
from about 10 to about 300 mg of BHA;
from about 1 to about 300 mg of sodium benzoate; and from about 10 to about 300 mg of propyl gallate.
from about 10 to about 300 mg of BHT;
from about 10 to about 300 mg of BHA;
from about 1 to about 300 mg of sodium benzoate; and from about 10 to about 300 mg of propyl gallate.
47. The method of claim 47 wherein said supplement further includes in combination:
from about 1 to about 20 mg of glutathione;
from about 5 to about 100 mg of cysteine HCl;
from about 1 to about 20 mg of methionine;
from about 1 to about 20 mg of glutamine; and from about 1 to about 20 mg of taurine;
from about 1 to about 20 mg of glutathione;
from about 5 to about 100 mg of cysteine HCl;
from about 1 to about 20 mg of methionine;
from about 1 to about 20 mg of glutamine; and from about 1 to about 20 mg of taurine;
48. The method of claim 46 wherein said supplement further includes from about 10 to 100 mg of PABA.
49. The method of claim 46 wherein said supplement further includes from about 10 to about 1000 mg of polyunsaturated fatty acids having an EPA:DHA ratio of about 18:12.
50. The method of claim 46 wherein said supplement further includes from about 100 to about 300 i.u. of superoxide dismutase.
51. The method of claim 50 wherein said supplement further includes from about 100 to about 300 i.u. of catalase.
52. The method of claim 46 wherein said supplement includes from about 10 to about 100 mg of a bioflavonoid.
53. The method of claim 46 wherein said supplement further includes:
from about 1000 to about 3000 i.u. of vitamin A;
from about 2500 to about 7500 i.u. of beta carotene;
and from about 10 to about 100 i.u. of vitamin E.
from about 1000 to about 3000 i.u. of vitamin A;
from about 2500 to about 7500 i.u. of beta carotene;
and from about 10 to about 100 i.u. of vitamin E.
54. The method of claim 46 wherein said supplement further includes at least the minimum daily requirement in man of:
vitamin C;
folic acid;
vitamin B,;
vitamin B2;
niacinamide;
vitamin B6;
vitamin B12;
vitamin D3;
biotin;
pantothenic acid vitamin K1.
vitamin C;
folic acid;
vitamin B,;
vitamin B2;
niacinamide;
vitamin B6;
vitamin B12;
vitamin D3;
biotin;
pantothenic acid vitamin K1.
55. The method of claim 54 wherein said supplement further includes at least the minimum daily requirement in man of a pharmaceutically acceptable mineral salt of:
calcium;
iodine;
potassium;
iron;
magnesium;
copper;
zinc;
manganese;
chromium;
molybdenum;
selenium;
vanadium;
silicon; and boron.
calcium;
iodine;
potassium;
iron;
magnesium;
copper;
zinc;
manganese;
chromium;
molybdenum;
selenium;
vanadium;
silicon; and boron.
56. The method of claim 54 wherein said supplement further includes from about 5 to about 100 mg of inositol.
57. A method for preventing cancer in a human subject, the method including the step of administering daily an oral sustained release tablet including the daily dietary multi-vitamin and mineral supplement for a human including about 50 mg of BHA.
58. A method for preventing cancer in a human subject, the method including the step of administering daily an oral sustained release tablet including the daily dietary multi-vitamin and mineral supplement for a human including about 50 mg propyl gallate.
59. A method for preventing cancer in a human subject, the method including the step of administering daily an oral sustained release tablet including the daily dietary multi-vitamin and mineral supplement for a human including in combination:
about 50 mg of BHT;
about 50 mg of BHA;
about 4 mg of sodium benzoate; and about 50 mg of propyl gallate.
about 50 mg of BHT;
about 50 mg of BHA;
about 4 mg of sodium benzoate; and about 50 mg of propyl gallate.
60. The method of claim 59 wherein said supplement further includes in combination:
about 10 mg of reduced L-glutathione;
about 50 mg of L-cysteine HCl;
about 10 mg of DL-methionine;
about 10 mg of L-glutamine; and about 10 mg of taurine;
about 10 mg of reduced L-glutathione;
about 50 mg of L-cysteine HCl;
about 10 mg of DL-methionine;
about 10 mg of L-glutamine; and about 10 mg of taurine;
61. The method of claim 59 which further includes from about 10 to 100 mg of PABA, and from about 5 to about 50 mg of calcium pantothenate.
62. The method of claim 59 which further includes about 500 mg Omega-3 fish oil having an EPA:DHA ratio of about 18:12.
63. The method of claim 59 wherein said supplement further includes about 150 i.u. of superoxide dismutase.
64. The method of claim 63 wherein said supplement further includes about 150 i.u. of catalase.
65. The method of claim 64 wherein the superoxide dismutase and catalase are from a food concentrate.
66. The method of claim 59 wherein said supplement includes about 50 mg a bioflavonoid.
67. The method of claim 59 wherein said supplement further includes:
about 2000 i.u. of vitamin A acetate;
about 5000 i.u. of beta carotene;
about 100 i.u. of vitamin E, DL alpha tocopheryl acetate;
about 250 mg calcium ascorbate; and about 200 mg of potassium sorbate.
about 2000 i.u. of vitamin A acetate;
about 5000 i.u. of beta carotene;
about 100 i.u. of vitamin E, DL alpha tocopheryl acetate;
about 250 mg calcium ascorbate; and about 200 mg of potassium sorbate.
68. A method for preventing cancer in a human subject, the method including the step of administering daily an oral sustained release tablet including the daily dietary multi-vitamin and mineral supplement for a human including, in combination, about 50 mg of BHT, and about 2000 i.u. of vitamin A acetate.
69. A method for preventing cancer in a human subject, the method including the step of administering daily an oral sustained release tablet including the daily dietary multi-vitamin and mineral supplement for a human including, in combination, about 50 mg of BHT, and about 5000 i.u. of beta carotene.
70. A method for preventing cancer in a human subject, the method including the step of administering daily an oral sustained release tablet including the daily dietary multi-vitamin and mineral supplement for a human including, in combination:
at least one antioxidant selected from the group consisting of BHT, BHA, propyl gallate, and sodium benzoate;
vitamin A;
vitamin E; and beta carotene.
at least one antioxidant selected from the group consisting of BHT, BHA, propyl gallate, and sodium benzoate;
vitamin A;
vitamin E; and beta carotene.
71. The method of claim 70 wherein said supplement further includes a pharmaceutically acceptable salt of selenium.
72. The method of claim 71 wherein said supplement further includes, in combination, at least one amino acid selected from the group consisting of reduced L-glutathione, L-cysteine HCl, DL-methionine, L-glutamine, and taurine.
73. A method for preventing cancer in a human subject, the method including the step of administering daily an oral sustained release tablet including the dietary supplement comprising, in combination:
about 2000iu of vitamin A acetate;
about 5000iu of beta carotene;
about 30iu of vitamin E, DL alpha tocopheryl acetate;
about 250mg of calcium ascorbate;
about 400mcg of folic acid;
about 1.5mg of vitamin B1;
about 1.75mg of vitamin B2;
about 20mg of niacinamide;
about 2mg of vitamin B6;
about 6mcg of vitamin B12;
about 600iu of vitamin D3;
about 30mcg of biotin;
about 10mg of calcium pantothenate; and about 25mcg of vitamin K1;
about 100mg of dicalcium phosphate;
potassium iodide sufficient to supply about 150mcg iodine;
potassium chloride sufficient to supply about 40mg of potassium;
ferrous fumarate sufficient to supply about 20mg of iron;
magnesium oxide sufficient to supply about 100mg of magnesium;
copper oxide sufficient to supply about 2mg of copper;
zinc oxide sufficient to supply about 15mg of zinc;
manganese gluconate sufficient to supply about 2mg of manganese;
chromium (+3)chloride sufficient to supply about 25mcg of chromium;
sodium molybdate sufficient to supply about 25mcg of molybdenum;
sodium selenate sufficient to supply about 25mcg of selenium;
sodium metavanadate sufficient to supply about 10mcg of vanadium;
sodium metasilicate sufficient to supply about 10mcg of silicon;
about 2mg of boron;
about 4mg of sodium benzoate;
about 250mg of calcium carbonate;
about 100mg of calcium citrate;
about 200mg of potassium sorbate\sorbic acid;
about 40mg of PABA;
about 200mg of Omega-3 fish oil;
about 50mg of inositol;
about 200iu of superoxide dismutase;
about 200iu of catalase;
about 200mg of BHT;
about 200mg of BHA; and about 50mg of a flavone; and about 50mg of propyl gallate.
about 2000iu of vitamin A acetate;
about 5000iu of beta carotene;
about 30iu of vitamin E, DL alpha tocopheryl acetate;
about 250mg of calcium ascorbate;
about 400mcg of folic acid;
about 1.5mg of vitamin B1;
about 1.75mg of vitamin B2;
about 20mg of niacinamide;
about 2mg of vitamin B6;
about 6mcg of vitamin B12;
about 600iu of vitamin D3;
about 30mcg of biotin;
about 10mg of calcium pantothenate; and about 25mcg of vitamin K1;
about 100mg of dicalcium phosphate;
potassium iodide sufficient to supply about 150mcg iodine;
potassium chloride sufficient to supply about 40mg of potassium;
ferrous fumarate sufficient to supply about 20mg of iron;
magnesium oxide sufficient to supply about 100mg of magnesium;
copper oxide sufficient to supply about 2mg of copper;
zinc oxide sufficient to supply about 15mg of zinc;
manganese gluconate sufficient to supply about 2mg of manganese;
chromium (+3)chloride sufficient to supply about 25mcg of chromium;
sodium molybdate sufficient to supply about 25mcg of molybdenum;
sodium selenate sufficient to supply about 25mcg of selenium;
sodium metavanadate sufficient to supply about 10mcg of vanadium;
sodium metasilicate sufficient to supply about 10mcg of silicon;
about 2mg of boron;
about 4mg of sodium benzoate;
about 250mg of calcium carbonate;
about 100mg of calcium citrate;
about 200mg of potassium sorbate\sorbic acid;
about 40mg of PABA;
about 200mg of Omega-3 fish oil;
about 50mg of inositol;
about 200iu of superoxide dismutase;
about 200iu of catalase;
about 200mg of BHT;
about 200mg of BHA; and about 50mg of a flavone; and about 50mg of propyl gallate.
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US47564190A | 1990-02-05 | 1990-02-05 | |
US07/475,641 | 1990-02-05 | ||
PCT/US1991/000719 WO1991011117A2 (en) | 1990-02-05 | 1991-02-04 | Dietary supplements comprising vitamins and minerals |
USPCT/US91/00719 | 1991-02-04 |
Publications (1)
Publication Number | Publication Date |
---|---|
CA2074527A1 true CA2074527A1 (en) | 1991-08-06 |
Family
ID=26782931
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA002074527A Abandoned CA2074527A1 (en) | 1990-02-05 | 1991-02-04 | Dietary supplements comprising vitamins and minerals |
Country Status (1)
Country | Link |
---|---|
CA (1) | CA2074527A1 (en) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20220062147A1 (en) * | 2020-09-03 | 2022-03-03 | Bottled Science Limited | Skin Care Formulation for Treatment of Cellulite |
-
1991
- 1991-02-04 CA CA002074527A patent/CA2074527A1/en not_active Abandoned
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20220062147A1 (en) * | 2020-09-03 | 2022-03-03 | Bottled Science Limited | Skin Care Formulation for Treatment of Cellulite |
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